A 49-year-old man developed speech disturbance and an unsteady gait. His mother had similar symptoms. He went to the hospital at the age of 52 years. The neurological examination disclosed saccadic eye movement, slurred speech, poor coordination, and wide-based and poor tandem walking. Deep tendon reflexes were normal and no pathological reflexes were noted. His Scale for the Assessment and Rating of Ataxia (SARA) score was 13. Brain magnetic resonance imaging (MRI) revealed a mild cerebellar atrophy with widening of cerebellar sulci (Fig. ). Genetic analysis revealed a mutation of −16 G>T q.22 and insertion of a penta-nucleotide repeat expansion (3.3 kb). The patient's mother showed the same mutation and repeat expansion of SCA31. He was diagnosed with SCA31. Differential diagnoses revealed no signs of metabolic or inflammatory etiologies. The cerebellar symptoms gradually worsened. His SARA score was 21 at the age of 62 years.
Fourteen years later at the age of 63 years, he suddenly developed paraplegia, as well as bladder and rectal disturbance. On admission, the general physical examination was normal. His past medical history included diabetes mellitus. Neurological examinations revealed saccadic eye movement, slurred speech, poor coordination, and muscle weakness of grade 1/5 affecting the lower limbs. He had no disturbance in the visual field and acuity. Deep tendon reflexes were absent in the lower limbs without pathological reflexes. There was loss of position and vibration sense combined with hypesthesia below T4. He had bladder and rectal disturbances. His SARA score was 32. The Expanded Disability Status Scale (EDSS) score was 8.5. Findings from routine serum studies, including blood chemistry and enzymes, were normal except for a HbA1c of 6.3%. He had normal or negative studies for HTLV-1, serum angiotensin converting enzyme, syphilis serology, and PR3- and MPO-ANCA. Cerebrospinal fluid analysis revealed a cell count of 12/ml (100% monocytes) with an increased protein concentration of 64 mg/dl and a myelin basic protein level of 754 mg/dL. Brain MRI showed high-intensity areas in the right posterior horn as well as the left anterior and posterior horns on diffusion-weighted (Fig. ), fluid-attenuated inversion recovery (FLAIR) (Fig. ), and T2-weighted image (T2WI). Spinal MRI on T2WI revealed long lesions extending from Th1/2 to Th11 (Fig. ). Axial T2WI at the level of Th6/7 showed high-signal intensity in the central part of the cord (Fig. ). The patient was treated 3 times with high-dose methylprednisolone (1,000 mg/day for 3 days). His serum was positive for anti-AQP4 antibody (cell-based assay) 25 days after the onset. He was diagnosed with NMOSD and treated with immunoadsorption plasmapheresis and followed up with daily prednisolone (30 mg). Follow-up brain MRI on T2WI and FLAIR 50 days after the onset showed slowly diminishing high-intensity areas in the right posterior horn and left anterior and posterior horns. However, follow-up spinal MRI had no change. He was bedridden and the paraplegia persisted. He discharged to another hospital for rehabilitation 3 months after the onset with a low-dose daily prednisolone (10 mg). His EDSS score was still 8.5.


A 60-year-old man developed pain in the left eye 3 days prior to his first visit. At the ophthalmological consultation, he negated any previous disorders, except a history of migraine, and was not taking any prescription medication. The patient displayed a slight exophthalmos of the left eye. BCVA was 0.8 in the right eye and 1.0 in his left eye. A fundus examination revealed a normal optic disc and retina in both eyes. The patient did not receive any treatment except tear substitution eye drops. Laboratory testing included determination of hemoglobin (HGB), glucose, C-reactive protein (CRP), thyroid-stimulating hormone (TSH), thyroxine (T4), and erythrocyte sedimentation rate (ESR), and results from all tests were normal. An orbital MRI with and without intravenous contrast carried out 3 weeks later revealed moderately increased signal intensity in the optical nerve sheaths, especially on the left side, in line with what is seen in OPN. The MRI also showed increased signaling in the retrobulbar fat. No swelling of the extraocular muscles was evident.
The eye pain had subsided at a new visit 2 months after the initial consultation. Visual acuity was measured 2, 5, and 12 months after the first visit; corrected visual acuity was 1.0 in both eyes on these examinations. Visual field and color vision tests were normal on all three follow-up examinations. Fundus examinations were performed on all three visits and did not reveal anything abnormal.


A 60-year-old male experienced dimmed vision in his left eye for 3 days prior to his first visit. The patient negated any other symptoms, including pain and diplopia. He had a history of two previous occurrences of possible ON – 30 years ago in his left eye and some 10 years later in his right eye. The patient had a history of hypertension and was currently on antihypertensive drugs. No relative afferent pupillary defect (RAPD) was present at his first examination. BCVA was 0.65 in the right eye and 0.5 in his left eye. A fundus examination revealed an atrophic and excavated disc in his right eye. An optic disc edema was present in his left eye. Retina was normal in both eyes. Laboratory tests for sarcoidosis, syphilis, and giant cell arteritis were analyzed, including determination of HGB, blood count, serum calcium, ESR, angiotensin-converting enzyme (ACE), Venereal Disease Research Laboratory (VDRL), and Wassermann reaction (WR). All tests were normal or negative. Visual field and color vision were analyzed 3 days later; visual field test showed arcuate inferior defects in both eyes, with equivalent neural capacity of 67% in his right eye and 58% in his left eye. A Sahlgren’s saturation test (SST) color vision test revealed a more defective color vision in his left (20) than in his right (15) eye.
An orbital MRI carried out 1 week later revealed increased signal intensity in the parts of the left optical nerve sheath, possibly indicating OPN. The MRI also showed increased signaling in the retrobulbar fat of the left eye. No increased swelling of the extraocular muscles was evident.
The patient received a course of prednisone, 60 mg/day, which was tapered over 1 month, at which time he was examined again. BCVA was 1.0 in the right eye and 0.65 in his left eye. The optic disc edema had subsided substantially since the last fundus examination 1 month earlier. He received a new course of prednisone, starting with 25 mg/day, which was tapered to 7.5 mg/day until his next visit 2 months later. His BCVA was 1.0 in his right eye and 0.65 in his left eye.
Visual field testing again showed arcuate inferior defects in both eyes and abnormal thresholds, with equivalent neural capacity of 69% in his right eye and 61% in his left eye. A new MRI showed a slight regression of the enhancement around the left optical nerve since the last MRI. The results of a fundus examination revealed a pale papilla in both eyes. He remained on 7.5 mg/day prednisone, which was tapered over 14 weeks. At a new consultation 4 months later, BCVA was 1.0 in the right eye and 0.5 in his left eye.


A 58-year-old woman experienced sudden deterioration of vision in her right eye, 2 weeks prior to her first visit. The patient negated any other symptoms related to her eyes, including pain and diplopia. The patient had a history of pain-related symptoms in her arms and negated taking any medicines regularly.
An initial eye examination determined BCVA to be 1.0 in her left eye, whereas she was only able to distinguish hand movement in her right eye. No RAPD was evident at this first examination. No proptosis or enophtalmus was present. A fundus examination revealed that both eyes had vital optic discs and normal retinas. Initial laboratory tests revealed a high ESR (22 mm/h), a slightly increased CRP (8 mg/L), and normal HGB and creatinine. The patient negated head pain, scalp tenderness, and jaw pain.
An orbital MRI was carried out 3 weeks after her initial visit and showed a suspected increase in fluid around the distal part of the optical nerve of the right eye, along with increased signaling. The pituitary gland also displayed increased signaling. The results were interpreted as being suggestive of OPN. The patient received a course of prednisone, starting with 60 mg/day for 5 days, 50 mg/day for 10 days, and 40 mg/day until her next appointment 3 months after her initial examination.
At the follow-up, an examination determined BCVA to be 1.3 in her left eye and <0.5 in her right eye. Because of severe side effects, the prednisone was tapered to 5 mg/day at her next visit 6 weeks later. BCVA was determined to be 1.0 in her left eye and 0.5 in her right eye. Color vision was assessed and found to be defective in her right eye (red light seen as pink). Prednisone was tapered out completely during the next 10 days. A new MRI showed increased signaling in the right optic nerve and right nerve sheath.
At a new examination 4 months later (8 months after her first visit), BCVA was unchanged. A visual field test of her right eye revealed a lower arcuate scotoma (Humphrey field test, visual field index [VFI] of 94%). Fundus examination revealed a pale papilla in her right eye compared to the left. The macula appeared to be normal.
A MRI of the sella turcica area and a chest x-ray was conducted. No pathological changes were observed. Further laboratory tests included markers for sarcoidosis (ACE), syphilis (WR, VDRL), and inflammation. Besides a slightly elevated haptoglobin, results did not support any increase in inflammatory activity.
Her symptoms were unchanged at her next ophthalmologic examination 10 months later (one and a half years after her first visit), once again showing a paler papilla in her right eye compared to her left. A RAPD was present in her right eye.
At her last eye examination, 18 months after the initial contact, the optic disc in her right eye was found to be pale and slightly atrophic compared to the left eye. BCVA was unchanged at 1.0 in her left eye and 0.5 in her right eye. RAPD was present.


A 26-year-old woman presented with a 2-week history of cold-like symptoms prior to her first visit. She described having had 5 days of movement-associated eye pain and 3 days of dimmed vision in her left peripheral visual field. The patient also stated having a headache. No previous history of eye disorders was acknowledged. She was taking antibiotics (phenoxymethylpenicillin and chloramphenicol eye drops) for her symptoms.
No RAPD was present at the initial examination. BCVA was 1.3 in the right eye and <1.0 in her left eye. The results of a fundus examination showed a normal retina, papilla, and macula in both eyes. An SST color vision test did not reveal any abnormalities (0p). A confrontation visual field exam revealed a possible inferior temporal defect in the left eye. The overall lack of findings in the examination did not lend support for any medical treatment.
Two weeks later, her vision deteriorated during a trip abroad. She could only perceive hand waving on her right eye and finger counting on her left. An MRI scan of the spinal cord, brain, and orbita revealed increased signal intensity in the optical nerve sheaths of both eyes, suggesting OPN. There was no evidence of any other abnormalities in the brain or spinal cord. She was being treated with methylprednisone 1 g/day for 5 days and prednisone 50 mg until her next examination 2 weeks later.
At this visit, the patient reported that her vision had normalized and that the pain had disappeared. BCVA was 1.3 in the right eye and 1.6 in her left eye. No RAPD was present. A visual field test did not demonstrate any irregularities on either eye (Humphrey field test, VFI was 100% in right eye and 98% in left eye). An SST color vision test suggested slightly more defective color vision in her right (15) than in her left (10) eye. As was the case at her first visit, a fundus examination showed a normal retina, papilla, and macula in both eyes. Except a small bulge on her left iris, possibly an iris cyst, nothing abnormal was found. Her prednisone treatment was tapered out during a period of 1 month.
Five weeks later, the woman contacted the hospital and described similar symptoms as earlier, including a severe headache coupled with eye movement. Her steroid treatment had been completed 1 week earlier. No RAPD was present. A visual field test revealed a defect in the lower quadrants of her right eye (Humphrey field test, VFI was 96% in the right eye and 98% in the left eye). A fundus examination again showed a normal retina, macula, and papilla. Steroid treatment was reinstated with 40 mg/day of prednisone.
Three weeks later, the patient was recuperating and reported that her eye sight had improved. A fundus examination revealed nothing abnormal. Her prednisone dose was slowly tapered. Seven months after her first visit, BCVA was 1.3 in her right eye and 1.6 in the left eye. An eye examination revealed nothing abnormal except for a persisting visual field defect in her left eye.


A 58-year-old male presented with a 2-day history of dimmed vision on his left eye. He reported having had headaches and swollenness behind his left eye during the last week. The patient had undergone heart surgery after a myocardial infarction 9 months prior to his first visit. He was taking several prescription medications because of hypertension and stent implants in his heart. These included aspirin, ticagrelor, bisoprolol, candesartan, and atorvastatin. Except for a pollen allergy, he negated other disorders.
An eye examination revealed free eye motility in all directions and slight movement-associated pain in his left eye. BCVA was 1.0 in the right eye and 0.1 in his left eye. There was no diplopia. A RAPD was present in his left eye at the same examination. Color vision was affected in the left eye. The results of a fundus examination revealed a normal optic disc in the right eye, except adjacent ectopic myelin in the lower portion. Retina and macula were without signs of disease. Examination of the left eye revealed papillary edema. Macula and retina were normal except for small hemorrhage from a vessel in the lower fundus. Blood pressure was 150/90. Initial laboratory tests that included ESR, CRP, serum calcium, ACE, anti-nuclear antibodies (ANAs), anti-neutrophil cytoplasmic antibodies (ANCA), and syphilis screen were normal, except for a slightly elevated IgA test.
An MRI of the orbita was performed a week after his first visit to the clinic and revealed a slight edema surrounding the left optical nerve, fitting with OPN. At this time, the patient reported that his vision had normalized. Steroid treatment was therefore not initiated. Since his first visit, he reported having three episodes of lost vision in his previously unaffected right eye a few days earlier. Also present was minor pain in his left eye and a few shorter episodes of blurred vision.
At a new visit, 3 weeks after his first, vision had improved further. A slight RAPD was present in his left eye. A fundus examination revealed no edema on either eye. Two months after his initial visit, BCVA was 0.8 in his right eye and 1.0 in the left eye. A visual field test conducted at the same time revealed a small isolated central scotoma with a slightly elevated threshold in his left eye (Humphrey field test, VFI was 100% in right eye and 99% in left eye).


A 64-year-old woman experienced gradual visual loss for several months prior to her first examination. The woman had a 15-year history of systemic lupus erythematosus (SLE). In addition, she suffered from hypertension, hyperlipidemia, chronic obstructive pulmonary disease (COPD), sleep apnea, and a sense of unsteadiness, which had worsened during the last months. She was on several medications (aspirin, omeprazole, simvastatin, atenolol, ramipril, amlodipine, albuterol inhalation, budenoside, and formoterol inhalation). She negated eye pain. BCVA was 0.8 in both eyes. Both visual fields exhibited temporal defects (Humphrey field test). A fundus examination showed peripapillary atrophy in both eyes, but no sign of edema. An MRI with and without intravenous contrast performed 1 week later revealed an increased volume of fluid surrounding both optical nerves as well as increased signal intensity in the optical nerve sheaths, as seen in OPN. The MRI also showed increased signaling in the retrobulbar fat of the left eye and possible subcortical vasculitis. At a consultation, 1 week after the first visit, BCVA was unchanged since the last visit. Laboratory testing was done for sarcoidosis (ACE), syphilis (WR, VDRL), and neuromyelitis optica (NMO). In addition, ESR, CRP, HGB, and blood count were determined. Results showed a high or abnormal ESR, serum lysozyme, polyclonal IgG, and creatinine. Results for NMO antibodies, syphilis, and sarcoidosis markers were normal or negative. A chest X-ray did not find any sign of sarcoidosis. However, a slightly enlarged heart was observed, suggesting a developing heart failure. The woman was later administered intravenous corticosteroids (1 g ×2) and cyclophosphamide to treat her SLE. Shortly after, the woman was hospitalized due to cardiac arrhythmia. Warfarin and digoxin were prescribed, and the woman was discharged from the hospital some days later. Because of her arrhythmia, future treatment with corticosteroids was restricted.
At a new examination 3 months after her first visit, BCVA was unchanged. Results from eye field tests were still abnormal, with no certain change since the last examination. An SST color vision test showed more defective color vision in the left eye (80 p), compared to the right (30 p). Fundus examination showed no optic disc edema in either eye.
At a new consultation 2 months later, BCVA was still unchanged at 0.8 in both eyes. She was on prednisone (5mg/day) in addition to methotrexate (5 mg/week) and levetiracetam, which had been prescribed since her last visit. A fundus examination revealed peripapillary atrophy, but no signs of disc edema in either the left or the right eye. Visual field tests were abnormal (Humphrey field test, VFI was 61% in right eye and 71% in left eye). One month later, she was given injections of rituximab.
At the final eye examination 10 months after her first visit, BCVA was 0.8/0.65. A slight improvement of visual test results was observed (Humphrey field test, VFI was 83% in right eye and 74% in left eye). As noted previously, color vision was more defective in the left eye (35 p) compared to the right (20 p), although some improvement was seen since the last examination.


A 56-year-old woman with a history of diabetes, hypertension, and heart failure developed a gradual decrease in vision in her left eye over a 2-month period prior to her first examination. Two weeks prior to her first visit, she developed left eye pain, radiating upward. She negated headaches, diplopia, or problems with her right eye. She was currently on insulin, antihypertensive medication, and aspirin. The results of the first ophthalmologic examination revealed optic disc edema and RAPD in the left eye. Visual acuity was 0.8 in the right eye and 0.13 in the left eye.
Initial laboratory testing included syphilis serology, Lyme disease (Borrelia antibodies), determination of HGB, electrolyte status, ACE, blood count, CRP, and ESR. The results of all the tests were negative or normal except Lyme disease serology (IgG 239 (pos), IgM 9 (neg)), low ACE (2 U/L), and eosinophilic cells (high).
An MRI performed 1 week later revealed enlargement and enhancement in the left nerve sheath from the eye to the chiasma, in line with the findings seen in OPN ( and ).
At a new consultation 1 month after her first visit, BCVA was unchanged. A visual field test revealed a general constriction of the visual field of the left eye, with equivalent neural capacity of 99% in his right eye and 33% in his left eye. Fundus examination showed progression of the left optic disc edema (). RAPD was still present. New laboratory tests that included ESR, CRP, ACE, and sarcoidosis revealed nothing abnormal.
One month later, 2 months after her first examination, the left optic disc edema had regressed but an RAPD was still present. Visual acuity was unchanged since her last visit. Treatment with prednisone was initiated, 60 mg/day, which was tapered to 25 mg/day over 4 weeks when she was examined again.
At a fourth consultation, 3 months after her first visit, visual acuity was 0.8 in both eyes. A SST color vision test revealed that the patient had more defective color vision in her left eye (35 p), compared to the right (15 p). The optic disc edema was reduced. The steroid dose was tapered to 5 mg/day during 3 weeks. At this point, the patient suffered her first relapse with dimmed vision in her left eye. Fundus examination 1 week later revealed a pale papilla. BCVA was now 0.8 in her right eye and 0.4 in her left eye. Steroid dose was increased to 30 mg/day and tapered to 20 mg/day until the next appointment 2 weeks later. Some days later, the patient was hospitalized with arrhythmia due to hypercalcemia and hyperkalemia. At the new consultation, visual acuity was 0.8 in her right eye and 0.5 in her left eye.
The steroid dose was lowered with 2.5 mg per week. At 10 mg/day, she suffered a second relapse and received intravenous steroids. Her corticosteroid dose was increased to 30 mg/day in addition to azathioprine (150 mg/day). A fundus examination 3 months later revealed a normal optic disc with no edema. One month later, the steroid dose had been tapered to 17.5 mg/day. BCVA was 0.8 in both eyes. An SST color vision test revealed defective color vision in both the right (30 p) and the left eye (40 p). The fundus examination showed no sign of optic disc edema.
Four months later, it was suspected that the patient was suffering from sarcoidosis. Liver and spleen biopsies were positive for granulomas.
Four months later, she had a third relapse. She was taking 150 mg azathioprine and no corticosteroids at this time. Both eyes were affected; BCVA was 0.4 in her left eye and 0.65 in her right eye. A fundus examination revealed blurred borders of the optic discs in both eyes.
At a new consultation 2 months later, she remained on azathioprine, 150 mg/day, and was taken off corticosteroids. BCVA was 0.5 in her right eye and 0.65 in her left eye. Fundus examination showed no optic disc edema. A new MRI added support to the OPN diagnosis.


A 52-year-old male with end-stage renal disease and hypertension presented for his regular dialysis treatment. He was receiving three times weekly haemodialysis through a forearm arteriovenous fistula prescribed for 4 h and 15 min, with a blood flow of 400 mL/min and a dialysate flow of 800 mL/min. His dialysis included two dialyzers (Polyflux 210 H) in tandem because of high muscle mass.
At the beginning of treatment, the patient reported feeling well and had a blood pressure of 122/83 mmHg. After 1 h, the patient's blood pressure rose to 165/103 mmHg, and the dialysis machine alarm system was activated because venous pressure had dropped from 190 mmHg to 17 mmHg. Arterial pressure remained constant at −200 mmHg. The alarm was silenced and treatment resumed. Several minutes later, the dialysis machine alarm sounded, when venous pressure decreased to 11 mmHg. Arterial pressure was −140 mmHg. Again, the alarm was silenced and treatment resumed.
After ∼1 h of several cycles of resuming treatment after silencing the alarm for low venous pressures, the patient started to complain of substernal chest pain and shortness of breath; blood pressure was noted to be 198/110 mmHg. Haemodialysis was discontinued, and the patient was transferred to a hospital. On inspection of the dialysis equipment, it was noted that the tubing connecting the tandem dialyzers was kinked.
After arrival in the emergency department, the patient's plasma in blood samples obtained for laboratory testing were noted to be coffee-coloured, and the following significant laboratory values were obtained: haemoglobin 8.9 g/dL, haematocrit 15% (1 week prior to this event haemoglobin and haematocrit were 11.4 g/dL and 34.3%, respectively), potassium 4.8 mmol/L, total bilirubin 17.9 mg/dL, unconjugated bilirubin 14.9 mg/dL, lactate dehydrogenase 16764 U/L, aspartate aminotransferase 732 U/L and alanine aminotransferase 34 U/L.
A working diagnosis of intravascular haemolysis secondary to mechanical trauma to red blood cells from kinked haemodialysis tubing was made, and the patient was hospitalized. He received two units of packed red blood cells for severe anaemia and intravenous nicardipine for blood pressure control. All symptoms resolved. His haemoglobin stabilized with no signs of further haemolysis. LDH, bilirubin, AST all gradually returned to normal. Potassium remained in the normal range throughout his hospital stay. Haemodialysis was performed during hospitalization without tandem dialyzers. The patient was later discharged and received haemodialysis in the outpatient dialysis facility with stable haemoglobin and haematocrit.
We subsequently performed a controlled in vitro dialysis experiment to evaluate the effect of partial occlusion of blood lines at various sites, using saline and tandem dialyzers (). Partial occlusion of the arterial line before the blood pump (A) results in a rapid increase in negative arterial pressure and activation of the machine alarm when the pressure becomes more negative than 250 mmHg. The blood pump will immediately stop again, if restarted without correction of the partial occlusion. Partial occlusion of the blood line connecting the two dialyzers (B) results in a slow decline in the venous pressure to ∼15 mmHg and reversal of the trans-membrane pressure. In this experiment, as in our patient's treatment, it was possible to restart the blood pump without correction of the partial occlusion. After silencing the alarm, a slow decline in venous pressure to between 10 and 20 mmHg again occurred, and only after several minutes (2–4 min depending on the severity of the occlusion) did the dialysis machine again activate the alarm. Similar results were obtained by partial occlusion of the blood line connecting the second dialyzer and the venous pressure monitor (B). Partial occlusion of the tubing returning blood to the patient (C) after the venous pressure monitor resulted in a rapid rise in venous pressure and activation of the alarm when the pressure exceeded 250 mmHg. The blood pump would immediately stop again if restarted without correction of the partial occlusion.
Haemolysis is a well-recognized but rare complication of haemodialysis. Haemolysis during haemodialysis results from contamination of the water system, excessive heat or erythrocyte damage caused by the shear injury from blood line occlusion or small-sized dialysis needles. Most patients with acute haemolysis during haemodialysis complain of back pain, chest tightness and shortness of breath []. A port-wine appearance of blood in the venous blood line, a pink discolouration of the plasma in centrifuged blood samples and a marked fall in haematocrit are usually noted. Dramatic deepening of skin pigmentation has also been described [].
In routine haemodialysis, kinking of the blood tubing between the blood pump and dialyzer will not be detected, as the pre-pump arterial pressure monitor will not sense higher pressures encountered in this segment []. In tandem dialysis, blood traverses through two dialyzers connected in series by a blood line, before returning to the patient. This unique situation contains a connecting blood line which is normally not present in a routine haemodialysis treatment. It is this extra segment of tubing, distal to the blood pump but proximal to the venous pressure monitor, in which kinking will not be detected readily by the pressure monitors that present the increased risk of tandem dialysis. The venous pressure monitor detects lower positive pressures because of the decreased delivery of blood volume through the kink in the connecting segment.
In summary, we present a patient who was receiving haemodialysis through tandem dialyzers to achieve better clearance. He had a severe haemolytic reaction due to partial occlusion of the blood line between the two dialyzers. Nurses were able to repeatedly override the alarm and resume dialysis; consequently, the kink in the line was not immediately recognized. Our in vitro experiment, in which the alarm could be silenced and dialysis resumed, explains how it was possible for the dialysis treatment to be continued despite this partial occlusion. It is important for dialysis providers to visually inspect blood lines for occlusion, especially in areas in which the pressure monitors are less sensitive, such as the segment distal to the blood pump and proximal to the venous pressure monitor. Because of the extra segment of tubing in this area with tandem dialysis, extra caution is warranted. Low positive venous pressures are also a clue to the low blood return to the patient that occurs with kinking in this segment. Nurses, physicians and others involved in dialysis should be aware of this rare but life-threatening complication of the use of tandem dialyzers.
Conflict of interest statement. None declared.


Our patient was a 62-year-old male with a periampullary duodenal mass discovered incidentally during a surveillance esophagogastroduodenoscopy for Barrett’s esophagus. An endoscopic biopsy showed only duodenal mucosa with changes suggestive of peptic duodenitis. Subsequent endoscopic ultrasound revealed a 1.5 cm × 0.8 cm mass with a 1.2 cm × 0.8 cm periduodenal lymph node. A fine needle aspiration (FNA) biopsy and endoscopic tunneled biopsy of the duodenal mass was performed, which collectively showed features consistent with a neuroendocrine tumor. Computed tomography (CT) imaging demonstrated a well-circumscribed intraluminal duodenal mass (2.1 cm × 1.4 cm) with mild enhancement and no discernable pathologic lymphadenopathy (Figure ). Retrospective review of CT imaging from two years prior did not show an obvious mass. The patient was asymptomatic. His past medical history was significant for Barrett’s esophagus, as mentioned above, as well as hypertension, gastro-esophageal reflux disease, and hyperlipidemia. He had no smoking history and only light alcohol usage.
Two and a half months later, the patient underwent a pancreaticoduodenectomy, hepatic artery lymph node and portal lymph node excision, cholecystectomy, and partial gastrectomy (the pylorus appeared ischemic intra-operatively). The patient’s course was complicated by a pancreatic leak and a pulmonary embolism. CT imaging performed at 19 mo showed no evidence of disease recurrence, and a routine healthcare check at 30 mo revealed no clinical evidence of disease recurrence.
Cytological smear preparation (Diff-Quick and Papanicolaou stains) from the duodenal mass FNA demonstrated a cellular specimen composed of intermediate-sized, bland epithelioid cells with round to oval nuclei. Rare large ganglioid cells with eccentric nuclei and a prominent nucleolus were seen. A concurrent endoscopic tunneled biopsy contained three fragments of duodenal mucosa, one of which had a few nests of neuroendocrine tumor cells within the submucosa, which stained positively for CAM 5.2 and synaptophysin and negatively for chromogranin (Figure ).
Grossly, the resected surgical specimen included a portion of duodenum with a 2.0 cm × 1.3 cm × 0.7 cm nodule protruding into the lumen. Overlying mucosa was intact. The lesion was 2.0 cm proximal to the ampulla of Vater. On sectioning, the mass was tan-white with focal grey-black discoloration and confined to the submucosa (Figure ).
Microscopic examination revealed a submucosal nodule in the duodenum with three distinct cell populations. Epithelioid endocrine cells were arranged in trabeculae and nests interspersed with spindled sustentacular cells. Gangliocytic cells were scattered throughout (Figure ). The spindle cell population stained positively for S-100, the gangliocytic cells stained positively for calretinin, and the epithelioid cells stained positively for chromogranin and synaptophysin. No mitotic figures were identified. Ki-67 immunohistochemical stain showed a proliferative index of 2% within the tumor cells. Within the primary tumor, CD117 immunohistochemical staining demonstrated up to 15 mast cells per high power field (hpf) focally, with most areas having 1 to 5 per hpf (Figure ). Within the lymph node metastasis, up to 7 mast cells per hpf were identified, while most areas had only 1 to 2 per hpf.
There was no intratumoral lymphovascular or perineural invasion identified, nor was there invasion into the adjacent pancreatic parenchyma. The hepatic artery lymph node and portal lymph node were also free of disease. Metastatic tumor was discovered in three of eight periduodenal lymph nodes (Figure ). Metastases stained similarly to the primary with regard to S-100, chromogranin, and synaptophysin, but stained negatively for calretinin.
Using PubMed, EMBASE, EBSCOhost MEDLINE and CINAHL, and Google Scholar databases, we searched for cases of GP with regional and distant metastases using variations on the key word/phrases “gangliocytic paraganglioma”, “lymph nodes”, “metastasis”, and “distant spread”. We included only cases with at least an abstract written in English or French. Four of the included cases were published as poster presentation abstracts at national and international conferences. Two poster presentation abstracts were not included due to either insufficient patient data or citation information. Finally, we excluded one case which was sited in other literature reviews, as it reported the presence of only two cellular components[].
Our literature search produced 31 cases of GP with metastatic disease (30 with at least regional lymph node involvement and one with only a single metastasis to the manubrium) (Table ). In 28 cases, lymph node involvement/metastatic disease was present at the time of initial diagnosis (26 cases with disease spread present in initial surgical resection; 1 case with regional disease diagnosed on follow-up surgery for positive margins[]; 1 case with regional disease diagnosis on pancreaticoduodenectomy with lymph node dissection performed after a local resection demonstrated tumor with muscularis mucosa invasion and lymphovascular space invasion[]), while metastatic disease/lymph node involvement was diagnosed on follow-up surveillance in 2 cases[,]. Of the 28 cases with initial synchronous metastases/regional disease, 14 reported preoperative imaging that was suspicious for disease spread[-], while in 2 cases regional disease was discovered intraoperatively with frozen section confirmation, prompting a pancreaticoduodenectomy[,]. In 29 cases, the primary lesion occurred in the duodenum. Fourteen were in the duodenal ampulla, 6 were periampullary, and 8 were in the 2nd portion or the junction between the 2nd and 3rd portions of the duodenum, and 1 was in the 3rd portion of the duodenum. Two primary tumors occurred in the head of the pancreas[,]. We included only cases with histological evidence of regional spread/metastatic disease.
Clinical findings: Among the 31 patients studied, age at presentation ranged from 16-74 years, with 77% (24/31) presenting in the 5th-7th decade of life. There was a male predominance, with a male to female ratio of 19:12. The most common presenting symptoms were abdominal pain (55%) and gastrointestinal bleeding or the resultant symptomatic anemia (42%). Eight patients presented with weight loss as one of their symptoms (26%). One patient with a pancreatic primary presented with steatorrhea[], while the other presented with jaundice[].
Management: Twenty-five of the 31 patients with regional spread/metastatic disease underwent a pancreaticoduodenectomy, 4 of which occurred following local resection. In one case, massive hematemesis prompted an exploratory laparotomy and local resection of tumor, which was found to have muscularis mucosa invasion and lymphovascular space invasion[]. In another case, pancreaticoduodenectomy was performed after local resection demonstrated positive margins[]. In the third case, pancreaticoduodenectomy followed resection of an 11 cm multiloculated retroperitoneal mass, which was determined to be a lymph node containing metastatic PG. Further workup revealed a 2 cm periampullary submucosal mass in the duodenum[]. In the fourth case, regional lymph node involvement was found in the initial local resection, as well as in the secondary resection[].
Four of the 31 patients were treated with local resection only, one of which underwent initial local resection of the primary tumor and lymph node metastasis with no signs of recurrence over a 20-mo follow-up period[]. The second patient presented with gastrointestinal complaints and was found to have a partially calcified mass in the liver and abdomen, which was initially diagnosed as metastatic neuroendocrine carcinoma. Later testing revealed a duodenal lesion extending posteriorly to the pancreas with lymph node and liver involvement. Subsequently, the patient underwent resection of the duodenal lesion, retropancreatic mass, part of the hepatic lesions, and all enlarged portal lymph nodes. CT at 8 mo follow-up revealed a slowly enlarging residual liver lesion[].
One remarkable patient with innumerable liver metastases in addition to her lymph node metastases was treated with adjuvant octreotide injections for residual disease left behind in her liver. At 27 mo follow-up, she had no significant change in residual disease[]. One patient with metastases to 6 of 7 sampled lymph nodes received adjuvant external beam radiotherapy and was disease-free at 12 mo[], while another patient with metastases in 3 of 9 sampled lymph nodes received 5 cycles of adjuvant chemotherapy (regimen not specified) with no evidence of disease at 36 mo[]. Finally, one patient expired secondary to metastatic disease burden. On initial pancreaticoduodenectomy, the patient was diagnosed with a periampullary GP metastatic to 7 of 16 regional lymph nodes. A follow-up CT at 4 mo revealed liver and pelvic cavity metastases, and radiotherapy (total dose of 5040 cGy) was performed with no improvement, followed by chemotherapy (combination of cyclophosphamide, vincristine, and dacarbazine) with no improvement. Nine months after the initial surgery, he underwent partial resection of the pelvic mass. His liver mass continued to enlarge, and he developed persistent ascites and fever and passed away 13 mo following his initial operation[]. This is the only case, to our knowledge, to follow a lethal course directly resultant from disease burden.
Follow-up: Of the 25 cases with available follow-up (including the case presented here), follow-up ranged from 0 (perioperative demise) to 131 mo after the initial surgical intervention. In most cases, patients remained without evidence of recurrent disease. Exceptions include the two with residual liver disease and the one with death secondary to metastatic disease as detailed above, as well as a patient whose 3-mo follow-up revealed a return of functional symptoms (elevated serum chromogranin A and serotonin at the time of initial diagnosis) and a CT demonstrating lymphadenopathy. This last patient was unfortunately lost to follow-up[]. In one case, the patient died from anuria and cardiorespiratory decompensation one week after initial surgery[]. The minority of case reports that discussed methods of surveillance described using CT scans, endoscopy, and physical examination.
Histopathological findings: Pathologic findings are briefly summarized in Table . All cases included describe three cellular components in the primary tumor: Epithelioid/endocrine-like, spindle-like, and ganglion-like. Of those, immunohistochemical staining of each cell type was described for 19[,,-,,-,,-]. Bucher et al[] describe a case of an ampullary “alveolar paraganglioma” with lymph node metastases, which has been included in other GP literature reviews. We have elected to omit this case from our comparative review, maintaining strict inclusion of only cases with the three separate components described[]. Twenty-one cases described histology of the metastatic disease, of which 15 reported all three components to be present.
Most frequently, mitotic figures were not found among tumor cells. When present, they consisted of no more than two per ten hpf. Necrosis was absent from the primary tumor site in all cases that included a histologic description. No cases were described as having a tumor capsule. Seventeen cases specified extent of primary tumor invasion and/or the presence of lymphovascular space invasion. Thirteen described invasion into at least the muscularis propria, and one invaded into the pancreas[]. Three cases reported lymphovascular space invasion[,,].
Of the cases describing immunohistochemical staining, those most commonly employed were S-100, chromogranin (CG), synaptophysin (SYN), somatostatin (SS), cytokeratin (CK), neuron-specific enolase (NSE), neurofilament (NF), and pancreatic polypeptide (PP). Nineteen cases described specific staining patterns among the three cell populations. Of note, SYN stained all epithelioid endocrine cells studied (18/18), NSE and SYN stained most ganglion-like cells studied (7/8 and 12/18 respectively), and S-100 stained all spindle-like/sustentacular cells studied (21/21).


A 20-year old male presented with complaint of pain for 8 months in left hip with limited range of motion. Pain usually becomes worse at night and was only relieved on medication. He had no previous history of any trauma. His X-ray hip joint was normal []. The patient then underwent both magneto resonance imaging (MRI) and a 99mTechnetium methylene diphosphonate (99mTc-MDP) bone scan. A 99mTc-MDP bone scan showed increased tracer uptake in left hip joint with a tiny faint focus of increased activity on neck of femur []. MRI showed significant joint effusion with abnormal focal signal intensity involving neck of left femur []. At this point, no specific diagnosis could be established. Patient underwent exploratory surgery but it was of no help. Post-operation his symptoms worsened further. Six months post-operatively, he underwent F-18 Fluoride positron emission tomography-computed tomography (PET-CT) bone scan that showed focal increased tracer uptake corresponding to a tiny calcified nidus along the anterior cortex of neck of femur with mild uptake in left hip joint and joint effusion. A diagnosis of osteoid osteoma with reactive synovitis was made []. Then, patient was taken up for radiofrequency ablation for osteoid osteoma and became pain free from the 4th day [].


A 16-year old male presented with severe pain and swelling of right elbow joint with restricted motion for past 4 months. The pain was not controlled by medication and was worse at night. Patient underwent both MRI and 99mTc-MDP bone scans. A 99mTc-MDP bone scan showed increased flow, blood pool, and tracer uptake in the region of right elbow []. MRI showed significant joint effusion and focus of low-signal intensity on T1 [] in olecranon fossa of right humerus. A review of bone scan also revealed a tiny focal uptake in olecranon fossa [arrow, []. Thus, a diagnosis of osteoid osteoma was made. Patient then underwent surgical removal of osteoid osteoma and histopathology confirmed the diagnosis [].


A 23-year old female presented with pain for 1 year in right hip joint, her pain became worse at night and was relieved with medication. She underwent an MRI 6 month back, which showed joint effusion and marrow edema in neck and trochanteric region of right femur. Possibility of infective/inflammatory pathology was considered. She was treated conservatively but was not relieved of pain. She underwent a repeat MRI after 6 months, which showed no significant interval change between two scans. For further evaluation, a bone scan was done that showed increased blood pool and 99mTc-MDP increased tracer uptake in proximal right femur noted []. A careful review of previous MRI showed a tiny focal signal abnormality in medial cortex of neck of femur []. A diagnosis of osteoid osteoma was suspected. For further evaluation, computed tomography (CT) was performed that showed small cortical lytic lesion with calcified nidus involving medial cortex of right femur []. The patient then underwent radiofrequency ablation for osteoid osteoma and became pain free [] on 2nd day of procedure.


A 49-year-old man was referred with a history of dry cough and exertional breathlessness of 2 months duration. Medical history was significant for type II diabetes mellitus (DM) treated with oral hypoglycemic agents. General examination revealed tachypnea. Respiratory system examination revealed bilateral rhonchi. Hemotological and biochemical blood parameters were normal. The chest X-ray was normal. CT of the thorax [] showed circumferential nodularity, calcification of the trachea-bronchial tree, and patchy consolidation in bilateral lower lobe areas. The differentials of tracheopathica osteochondroplastica (TPO), tuberculosis, sarcoidosis, and vasculitis were considered. Sputum evaluation was negative for acid fast bacilli (AFB). Spirometry was suggestive of an obstructive abnormality, with forced inspiratory volume in 1st second (FEV1) of 0.75 L (35% of predicted) with good bronchodilator reversibility. Fiberoptic bronchoscopy (FOB) demonstrated widespread nodularity of the entire trachea-bronchial tree [], extending to the segmental bronchi. Endobronchial biopsy (EBB) of the nodules revealed noncaseating granulomas on histopathology. EBB AFB culture was negative. Bronchial washings and post-scopy sputum were evaluated for GeneXpert, which did not detect Mycobacterium tuberculosis (MTB). Mantoux test was negative. Serum ACE level was 32 IU/ml. Perinuclear-Anti-Neutrophil-Cytoplasmic-Antibodies (P-ANCA) and Cytoplasmic-Anti-Neutrophil-Cytoplasmic-Antibodies (C-ANCA) were negative. A provisional diagnosis of sarcoidosis was kept. 18F-FDG-PET/CT [] was performed, which showed enhanced metabolic activity in the nodular circumferential wall thickening with calcification in the trachea, extending distally up to the main bronchi and proximal lobar bronchi. Summary of results has been provided in . The patient was treated with oral prednisolone (40 mg daily) with inhaled corticosteroids (ICS) and long-acting beta-2 agonist (LABA) combination administered through a pressurized metered dose inhaler (MDI). On 6-week follow up, the patient had complete resolution of symptoms, improvement in FEV1 by1500 ml, complete resolution of nodularity on bronchoscopy []; repeat 18F-FDG-PET/CT [] demonstrated resolution of hypermetabolism observed in the baseline scan, suggesting favorable metabolic response to therapy.


A 65-year-old, 50 kg, female presented with the complaints of progressive pain and swelling over the right lower limb for the past one week following a thorn prick. This was associated with a history of high-grade fever, chills, rigor, productive cough, and mild dyspnea. She was a known case of type 2 diabetes mellitus, for which she was taking oral hypoglycemic drugs. Laboratory workup showed that the wound was infected with methicillin-resistant Staphylococcus aureus and hence, intravenous linezolid was started. Further, the wound infection was spreading upward until the knee joint hence decided for above knee amputation. On examination, the patient was conscious, drowsy, responding to commands. She was pale, febrile with temperature of 101 F, pulse rate 113/min, blood pressure 130/80 mmHg, with a mild tachypnea. Her central nervous system and cardiovascular examination were normal. Her investigations showed that she was anemic with Hb 7.8, total count was 32,500, and her platelet count was 63,000. Her renal parameters were mildly elevated with a prothrombin time (international normalized ratio) of 1.4. Her glycemic control was poor capillary blood glucose trending >250 mg/dL. On considering ongoing sepsis in the presence of active infectious focus, it was considered to do above knee amputation for infection control and as a lifesaving procedure. Central neuraxial anesthesia was deferred because of low platelet count and lack of time of correction with platelet infusions. However, in view of difficult airway with active respiratory tract infection and severe wheeze, general anesthesia was considered relatively unsafe. We administered nebulized salmeterol with budesonide to optimize the respiratory system. We planned to take up this case under peripheral nerve block alone. Hence, we did femoral nerve and lateral femoral cutaneous nerve (LFCN) blocks in supine position and sciatic nerve block in prone position with a mixture of local anesthetics. Fifteen milliliters of 0.5% bupivacaine with 15 ml 2% lignocaine 1:200,000 adrenaline and 10 ml of normal saline was prepared. We used 15 ml (femoral), 15 ml (sciatic), and 3 ml (LFCN) of the mixture, respectively, under ultrasound guidance. Regarding femoral nerve, the ultrasound probe was placed just above inguinal ligament and the nerve was blocked 2 cm above the inguinal ligament. LFCN was blocked according to classically described technique. Switching the patient to prone position, the sciatic nerve was visualized at the subgluteal region between the ischial tuberosity and greater trochanter of the femur. On checking the sensory and motor components of two major nerves were blocked satisfactorily. On specific checking for obturator nerve, there was a loss of sensation on the medial side of the knee with decreased power of adductors. Surgery was uneventful with a minimal discomfort during maneuvering of the lateral thigh which settled with 40 mg of intravenous pethidine. Intraoperative one unit packed cell, with two units each of fresh frozen plasma and platelets, was transfused. Glycemic control was achieved with intravenous short-acting insulin, and further, it was maintained with sliding scale of short-acting insulin to keep random blood glucose at 150 mg%. Nebulized drugs were continued. Platelet count improved to 100,000 the next day. Her postoperative period was uneventful.


A 40-year-old man presented after a presumed marine animal sting on his neck while scuba diving in Curacao 6 weeks ago, when a fire coral fish stung his neck, with a wheal forming immediately at the site of the lesion. On the following day, he also developed left axillary adenopathy and a rash on his center chest without vesicles or purulence. He was initially prescribed 2 weeks of cephalexin due to concern for possible cellulitis. With antibiotics, his adenopathy nearly resolved; however, the rash remained. Associated symptoms included chest pain that was both pleuritic and reproducible upon palpation, generalized myalgia, intermittent shortness of breath, and malaise.
Pertinent physical exam findings included a maculopapular rash overlying the sternum with severe tenderness to palpation and mild right axillary adenopathy. Laboratory workup was notable for an erythrocyte sedimentation rate (ESR) of 42 mm/h and C-reactive protein of 4.08 mg/dL. Complete blood count showed mild microcytic anemia with hemoglobin of 13.4 g/dL, normal white blood count of 9,400/μL, and platelet count of 317,000/μL. Computed tomography (CT) scan of the chest suggested an inflammatory process at the sternum with mediastinal involvement, so that osteomyelitis could not be ruled out. Subsequent magnetic resonance imaging of the sternum revealed diffuse T1 marrow replacement and corresponding enhancing edema involving the sternum, suggesting extensive osteomyelitis. There was also an area of nonenhancement in the manubrium, suggesting necrotic bone (Fig. ), along with extensive phlegmon in the muscles spanning 9 cm × 5 cm (Fig. ) with multiple small abscesses and myositis.
The patient was taken to the operating room twice for extensive debridement of his left chest wall and was empirically started on vancomycin and cefepime. Wound culture eventually grew 1+ Propionibacterium, and the patient was discharged on a 6-week course of vancomycin and Meropenem with the presumed diagnosis of osteomyelitis.
A few days after discharge, the patient's sternal bone biopsy from prior debridement came back with an atypical lymphohistiocytic infiltrate suggestive of Hodgkin lymphoma. Repeat CT of the chest showed multiple large bilateral axillary lymph nodes, and so ultrasound-guided right axillary lymph node biopsy was performed; however, the pathology only showed large atypical cells. Flow cytometry did not find any monotypic B-cell population, and therefore, it was not suggestive of a lymphoproliferative disorder. Given the high suspicion of lymphoma at this point, positron emission tomography (PET)/CT was done and located a highly fludeoxyglucose-avid right axillary lymph node measuring 2.4 cm × 2.4 cm (Fig. ), in which excisional biopsy was performed. Pathology showed nodules of lymphocytes surrounded by fibrous bands, typical of classical Hodgkin lymphoma, nodular sclerosis variant (Fig. ). Reed-Sternberg cells and numerous lacunar cells were seen on a background of a mixed population of small lymphocytes (Fig. ). Immunohistochemistry revealed neoplastic cells positive for CD20, PAX5, CD30, and CD15, negative for CD45 and CD3, and Ki-67 positive in 40–50% of cells (Fig. ). Together, this confirmed the diagnosis of nodular-sclerosis classical Hodgkin lymphoma.
Repeat PET/CT 3 weeks later showed an increase of fludeoxyglucose activity with a standardized uptake value from 3.7 to 24.9 on one of the index axillary nodes. The number and size of bilateral cervical and axillary adenopathy also increased (Fig. ) consistent with lymphoma progression. Due to discontinuous involvement of the sternum, even though there was no disease below the diaphragm, the patient was determined to have Hodgkin lymphoma stage IVA. His international prognostic score was 3. The patient was started on an AVD (doxorubicin, vinblastine, and dacarbazine) chemotherapy regimen. Bleomycin was not added due to marginal diffusing capacity of the lung for carbon monoxide (DLCO). The plan was to add brentuximab later to the regimen.


A 66-year-old man visited a local hospital complaining of dizziness and was diagnosed with MM about five years ago. Quantitative immunoglobulins from serum revealed total IgA level of 6,340 mg/dl (normal 68~378 mg/dl) with decreased IgG and IgM levels. Both serum and urine immunofixation showed monoclonal gammopathy of IgA, lambda type. A bone marrow aspirate demonstrated 60% plasma cell infiltration, which confirmed a diagnosis of IgA lambda MM. The patient received two cycles of cyclophosphamide, dexamethasone, and thalidomide chemotherapy followed by autologous bone marrow transplantation and autologous peripheral blood stem cell transplantation. However, MM recurred after eight months with 11.2% of plasma cells in the bone marrow and eight courses of velcade and dexamethasone (VD) chemotherapy were conducted over nine months. And the MM recurred once again in the bone marrow and the mandible, so he received additional radiotherapy (RTx) on his mandible for ten times. After his RTx, another VD chemotherapy regimen was added to his therapy but the disease did not regress.
The patient presented with pruritic erythematous to purplish, rapidly growing, multiple grouped nodule with black pigmentations and purpura on the right forearm over one month (). Eight months before his skin lesions appeared, he underwent open reduction and internal fixation with plates and screws for fracture on his right forearm. Histopathologically, epidermal thinning and rete ridge flattening were observed without plasma cell infiltrationand dermal separation probably occurred as an artifact. Atypical cells with hyperchromatic nuclei and mild degree of mitoses and vessel dilatation are dispersed throughout dermis but more prominent in deeper dermis. Multiple plasma cell infiltration and necrosis were found in dermis () with monoclonality for lambda light chain (), which was consistent with cutaneous plasmacytoma. Additional immunohistochemical stains such as CD3, CD20, CD56, CD45, pan CK, CK20, CK7, S-100 protein, chromogranin, synaptophysin, TTF-1, and EBER were all negative in tumor cells. The cells were stained positive for CD138 (). The patient refused to be treated and died two months later.


A 48-year-old male hypertensive patient with no significant smoking history or alcohol abuse presented with complaints of cough and progressive exertional dyspnea for 3 years. Examination revealed clubbing and fine bibasilar “velcro” crepitations. The resting pulse oximetry saturation was 80%. Pulmonary function studies revealed a severe restrictive impairment with a severely reduced diffusion capacity. A high-resolution computed tomography (HRCT) of the chest showed predominantly bilateral basal subpleural interstitial thickening with honeycombing and traction bronchiectasis, a picture diagnostic of IPF [].[] A transthoracic echocardiography revealed normal chamber sizes, left ventricular ejection fraction of 62%, Grade I diastolic dysfunction, moderate tricuspid regurgitation, and an estimated mean pulmonary artery pressure of 50 mmHg. There was no evidence of an ASD or a PFO. He was advised to start oral prednisolone and was followed regularly but showed little symptomatic improvement. Therefore, it was gradually tapered off and he was given symptomatic and supportive treatment.
One year later, he presented with rapidly worsening dyspnea and cough over the past week with mucoid expectoration of about half a cup per day associated with low-grade fever. He had also noticed a worsening of breathlessness on assuming an upright position and felt relieved in a supine position. There was no pedal edema, raised jugular venous pressure, or other signs of heart failure. Examination revealed respiratory distress with cyanosis and a respiratory rate of 32/min with rapid and shallow breathing, a pulse rate of 130 min, and a normal blood pressure. The patient was afebrile and required oxygen with 50% venturi and additional nasal prongs to barely maintain a pulse oximetry saturation between 85 and 90%. Arterial blood gas analysis revealed a pH 7.39, PaCO2 43 mmHg, PaO2 45 mmHg, and HCO3− 26.1 mmol/L with normal serum electrolytes.
Laboratory investigations including hemogram, kidney biochemistry profile, and coagulation parameters were in the normal range. Liver function tests revealed normal bilirubin and alkaline phosphatase levels but elevated other liver enzymes (alanine aminotransferase 230 IU/L, aspartate aminotransferase 121 IU/L). Hepatitis panel – HbsAg, hepatitis C virus (IgM) and hepatitis A virus (IgM) – and HIV (serology) were negative. The electrocardiogram showed sinus tachycardia.
Chest radiograph [] revealed bilateral volume reduction with dense reticulonodular opacities in all the three zones and honeycombing in the lower zones. HRCT scan of the chest [] revealed bilateral intralobular and interlobular septal thickening and subpleural honeycombing with diffuse ground glass haze in both lower lobes. In view of his refractory hypoxemia and ground glass haze on CT scan, P. jiroveci infection was suspected and subsequently confirmed by Gomori methenamine silver stain done on sputum. Sputum was negative for acid-fast bacilli on two occasions. No other pathogen was isolated from sputum cultures. After a detailed discussion on the likely outcomes, the family opted against mechanical ventilation. Treatment was started with co-trimoxazole.
Due to a definite postural association of symptoms, cardiorespiratory parameters were monitored in the supine position, 1 min after assuming sitting position, and then again after returning to the supine position []. Oxygen administration was continued as above. Breathlessness was rated using the modified Borg scale. Assumption of sitting position resulted in tachycardia, tachypnea, and substantial desaturation associated with marked increase in breathlessness. Resumption of the supine position led to recovery toward baseline.
A final diagnosis of IPF with hypertension with PJP with Type I respiratory failure with POS was made. The patient succumbed to his illness after a week.


An 83-year-old man, who had undergone a left pneumonectomy for primary lung cancer 33 months earlier, presented in our clinic complaining of several weeks history of significant weight loss, dyspnea and a progressively increasing and painful swelling of his left chest. Physical examination revealed an impressively large, soft and balottable mass located at the level of the previous left thoracotomy (Fig. ). Chest computed tomography (CT)-scan showed extensive herniation of the post-pneumonectomy cavity through the rib spaces, contained by the pleura (Fig. A–D). The patient denied recent history of chest trauma or episodes of violent cough, and all laboratory tests, including inflammatory markers, were unremarkable. Given the size of the herniation and the patient’s progressively worsening symptoms, surgical treatment for this unusual condition was deemed necessary. Surgery was carried out via a standard postero-lateral thoracotomy at the level of the old incision. The massive pleural hernia sac was immediately evident (Fig. A) and, once opened, ~1700 ml pleural fluid of gelatinous consistence was aspirated. The herniation site was identified in the previously opened intercostal space, in an antero-lateral position (Fig. B). The large sac (21 × 18 cm2) was excised and removed (Fig. C), while the defect was repaired with a polypropylene mesh, fixed by interrupted sutures and covered with the edge of the adjacent serratus anterior muscle (Fig. D). Histology results of the pleural hernia specimen showed inflammatory changes and granulation tissue. Postoperative recovery was uneventful and patient was discharged with minimal pain after 72 h, with an elasticated vest to be worn for 6 weeks. At 6-month follow-up, patient is well and there is no evidence of recurrence.


A 52-year-old Caucasian male with history of bipolar disorder was brought in by his son to the emergency room (ER) following severe bilateral injuries to his eyes as an attempt to self-enucleate. The patient called his son to his bedroom after attempting to manually pull his eyes out with his fingers because he was instructed to do so by God and felt the need to cleanse myself from sin. The patient was transferred to the ER by ambulance and appeared calm. The son reports that the patient had been acting strange and displayed decreased appetite and increased wakefulness. He was noted to draw complex numerical pyramid schematics in a notebook, and endorsed that God was speaking to him more over the past week. He was diagnosed with bipolar disorder 18 years ago with most recent manic episode occurring 16 years ago, resulting in a failed suicide attempt by hanging and subsequent hospitalization. Since then, the patient followed up with an outpatient psychiatrist on Risperdal 1 mg every night (QHS) and lithium 900 mg QHS and was otherwise noted to be highly functional and performed well at a high functioning professional. The patient had no other history of self-harming behavior.
On mental status exam he appeared well groomed with good hygiene and was dressed appropriately for the weather. Speech was within normal limits for rate, rhythm, and volume. He exhibited normal psychomotor behavior; mood was good, and affect was inappropriately flat given the severity of his injuries. He related to his examiners in a nonchalant demeanor. His thought process was linear and goal-directed as evidenced by his stating I do not feel any pain or remorse, I feel I have done the right thing. What I was supposed to do and I am cleansed now. He endorsed auditory hallucinations of God’s voice, and denied visual hallucinations, paranoid ideation, and suicidal or homicidal ideations. He had no overt impairment of impulse control and was able to answer questions appropriately. His insight and judgment were impaired.
On ophthalmology exam the patient’s visual acuity (VA) was no light perception (NLP) for both eyes (OU). The patient’s eyes were found to have severe proptosis, extensive conjunctival lacerations and hemorrhage, and visibly avulsed extraocular muscles (). A CT scan of the orbits demonstrated small and irregular globes, air within the orbits, and intraocular hemorrhage (). Multiple foci of air and soft tissue stranding is also seen (). The optic nerves were on stretch with posterior tenting of the globe suggesting severe optic nerve injury. Due to the optic nerve injury, the patient was started on intravenous (IV) methylprednisolone to reduce orbital edema and optic nerve inflammation and placed on IV and topical antibiotics. He was taken to the operating room by ophthalmology to repair the conjunctival lacerations, reattach the extraocular muscles and to limit the exposure of his eyes by detaching his lateral canthal tendons and suturing his eyelids closed with tarsorraphies ().
Postoperatively, the patient was admitted inpatient for medical and psychiatric stabilization. The psychiatry team evaluated the patient and gave the diagnosis of bipolar mania with psychotic features, with the most recent episode constituted by hyperreligious delusions and command auditory hallucinations. When he arrived on the inpatient psychiatric unit he was disorganized, responded to internal stimuli, and expressed thoughts of self-harm such as cutting off his arm to further cleanse himself. As his lithium level was therapeutic on admission (1.22), his mood stabilizer was switched to Depakote 1500 mg QHS and Risperdal was increased to 1 mg twice a day (BID). An ophthalmic examination one week after surgery demonstrated NLP vision OU with nonreactive pupils OU and complete ophthalmoplegia. Over the course of 3 weeks he slowly gained insight to the extent of the damage he caused and expressed some regret. He was discharged in stable psychiatric condition with close outpatient psychiatric follow-up.


A healthy 17-year-old girl was admitted to the Department of Oral and Maxillofacial Surgery because of swelling on the left side of face since birth. Decreased mouth opening was reported. The patient showed no other anomalies on physical examination. Swelling was tender, firm, afebrile, nonfluctuant, noncompressible, nonpulsatile, and bony hard in consistency. It was extending from the upper border of zygomatic arch superiorly and medially up to body of zygoma []. Lateral and inferior borders of the swelling were not distinct. Patient also gave a history of surgery at the same site 16 years back when she was 1 year old. She had lost all the records pertaining to that surgery. She also informed that after her first surgery, the surgeon had asked her to come after 6 months for another surgery at the same site. She did not report back as she considered herself as well as treated and was totally symptomless. Now, again the reason for reporting to the doctor was the patient's concern of reduced mouth opening which she wanted to get corrected and also got obvious facial swelling which was making her esthetically compromised. Facial swelling had become obvious only within 6 months.
Axial computed tomography (CT) scan sections revealed a well-delineated variable density soft tissue lesion in left infratemporal and buccal space. The lesion was heterogeneously enhancing on contrast with areas of hypodensity and peripheral enhancement. The lesion was abutting the posterolateral wall of left maxillary sinus and medial aspect of left zygoma causing anterior and lateral displacement of the zygomatic bone. Posteriorly, the lesion was extending up to left ramus of mandible and between the pterygoid plates. CT scan features were consistent with a diagnosis of dermoid cyst [].
The cyst was entirely removed under general anesthesia. The excised specimen was submitted to the Department of Oral Pathology with the provisional diagnosis of dermoid cyst or epidermoid cyst. Gross examination of the lesion showed a dumbbell-shaped cystic mass with thick fibrous extension anteriorly. Cystic component measured 3.5 cm × 4.5 cm × 2.3 cm with the fibrous extension measuring 6.5 cm × 2.4 cm × 1.2 cm. On cut section of the cystic lumen, the yellow-colored granular material was seen and stained for cystic content []. The material showed the presence of cholesterol crystals and no keratin. Different bits from different parts of cystic wall as well as fibrous extension were kept for routine processing in the Department of Oral Pathology. Microscopically, a cystic lining which is thin and thick at places showed uniform fibrous connective tissue stroma supported a lining that contained foci of different types of epithelium: stratified squamous epithelium, intestinal type of epithelium, and single layer of tall columnar epithelium. In some parts, the cyst was surrounded by an external layer of smooth muscle [Figures and ].
The patient is kept on regular follow-up after every 3 months.


A 60-year-old man presented with 1-month history of hypoesthesia in the trunk below T4 sensory dermatome, progressive gait disturbance and thoracic girdle pain. On the neurological examination, he demonstrated sensory impairment below T5 dermatome and increased deep tendon reflex bilaterally. The patient did not have any previous history of trauma or spine surgery before.
Magnetic resonance (MR) imaging demonstrated an oval shaped and well defined IDEM mass lesion centered with compressing thoracic cord in T2–3 level. The lesion was iso-intensity on T1-weighted images (T1WI), relatively hyper-intensity on T2-weighted images (T2WI), and homogenous well enhancement of entire mass with considering dural tail sign on contrast-enhanced T1WI. There were signal voids, suspicious vascular structures around the tumor on T2WI. Additionally, extensive arachnoiditis on thoracolumbar region below the tumor level and small sized and round shaped syrinx on the conus medullaris were noted ().
The preoperative diagnosis was a meningioma due to homogeneous enhancement across the whole mass lesion and attached dura considered as dural tail sign. The patient underwent T2 total laminectomy and T3 subtotal laminectomy. On opening the dura, friable oval shaped, dark reddish colored mass compressing spinal cord was noted. The mass was covered by the thickened arachnoid membrane, and strongly matted and adherent to pia mater of thoracic cord and involving left T2 nerve root. There was an ill-defined boundary between the tumor and the thoracic cord without attaching to the dura. Careful dissections and coagulating the surrounding tissues were performed to divide and dissect the spinal cord and nerve root from the tumor under the microscope. There was some amount of bleeding by the violation of tumor capsule during resection. Cranial and caudal poles of the mass contained dilated vessels traveling along the direction of left T2 nerve roots. Complete resection was achieved with detachment of around neural components and coagulation of dilated vessels.
Histological examination revealed hemangioma consists of a myriad of tightly packed well-formed capillaries lined by a single layer of endothelial cells. There are also variably dilated cavernous formations within the clustered capillaries. Immuno-histochemical staining showed positive response on CD31 ().
The patient’s symptoms including gait disturbance and sensory change improved noticeably 2 weeks after the surgery.


A 31-year-old white male presented with a progressive spastic quadriparesis over 1-year duration. Four years previously, he had fallen from a horse into a tree called Mandacaru (Cereus jamaracu) in northeast Brazil. At the time of the injury, the patient had several skin wounds but no neurological symptoms or signs. Four years later, he presented with new onset of spastic tetraparesis characterized by motor 4/5 strength in the upper and lower limbs; he could only ambulate with assistance.
While plain radiographs of cervical spine revealed upper cervical kyphosis, computed tomography (CT) scan [] demonstrated a foreign body resembling a needle that entered the spinal canal through the left C3-C4 foramen. Magnetic resonance imaging (MRI) [] demonstrated extensive edema in the cervical spinal cord and enhancement with gadolinium of tissue surrounding the foreign body.
The needle was removed utilizing a left side approach to the left C3-C4 foramen. (Hodgson-like approach[] posterior-lateral view).
A 5-cm thorn was removed []; of interest, there was no cerebrospinal fluid (CSF) leak. The postoperative course was uneventful and he continued to improve over the next 6 months.


A 6-year-old, neutered male domestic shorthair (DSH) cat was seen at the VRCC for investigation and management of dysphonia and intermittent inspiratory stridor of 17 days’ duration. The cat was vaccinated against feline panleukopenia virus, feline calicivirus and FeHV-1, lived in a rural area and was reported to be a keen hunter. Routine haematology and serum biochemistry were unremarkable. Serum was negative for feline leukaemia virus (FeLV) p27 antigen, feline immunodeficiency virus (FIV) antibodies and feline coronavirus antibodies. Under general anaesthesia, full oropharyngeal and laryngeal examination identified laryngeal oedema with normal function. The cat was discharged with amoxicillin–clavulanic acid (Clavaseptin [Vetoquinol] 15 mg/kg PO q12h).
A week later, the cat re-presented with inspiratory dyspnoea and pronounced inspiratory stridor. No other abnormalities were found on physical examination, except for sinus bradycardia (heart rate ranging between 84 and 120 bpm). An atropine response test was positive, indicating that the bradycardia was likely due to high vagal tone. Neither skin lesions nor pyrexia were present.
Full oropharyngeal and laryngeal examination was repeated and identified a 1 cm right-sided para-laryngeal mass and oedema affecting the right arytenoid process. Biopsy samples were obtained for histopathology, and identified a cluster of epithelial cells with intracytoplasmic eosinophilic inclusion bodies, as well as an inflammatory infiltrate (). Quantitative PCR performed on scrolls from the formalin-fixed biopsies confirmed the presence of CPxV DNA within the sections. Thoracic radiographs and abdominal ultrasound excluded the presence of disseminated disease.
The cat was given supportive care, including oxygen and compound sodium lactate (Hartmann’s solution, 2 ml/kg/h IV). Feline rFeIFN-ω (Virbagen Omega; Virbac [1 MU/kg SC q24h for 3 days]), prednisolone (Prednicare [Animal Care] 0.5 mg/kg PO q24h), marbofloxacin (Marbocyl [Vetoquinol] 2 mg/kg IV q24h) and famciclovir (Famvir [Novartis] 62.5 mg PO q12h) were also administered. Following clinical improvement the cat was discharged.
Fourteen days after first presentation, full oropharyngeal and laryngeal examination revealed the lesion had grossly resolved, as had the previously reported clinical signs. A year after diagnosis, the cat was clinically well with no further episodes of stridor or dysphonia.


A 4-year-10-month-old, neutered male DSH cat presented to its primary veterinary practice with a history of focal superficial ulceration with associated oedema and swelling of the subcutaneous adipose tissue in the caudal mammary region; the cat had a temperature of 39.0°C. It had a history of being an avid hunter and was overweight at the time, with a body condition score of 7/9. The cat was treated with cefovecin (Convenia [Zoetis] 8 mg/kg SC) and oral meloxicam (Metacam [Boehringer Ingelheim] 0.05 mg/kg PO q24h).
Three days later the cat was re-presented. There had been no response to the previous treatment with the lesion worsening in appearance, which now had a widened area of ulceration, pronounced thickening and marked oedema of the underlying subcutaneous tissue. Oral clindamycin (Antirobe [Zoetis] 5.5 mg/kg q12h) was commenced in addition to the current medications.
A further 2 days later, the area of ulceration affecting the ventral abdomen had progressed to a necrotic eschar (), with a concurrent increase in lethargy and discomfort. There were also multiple small raised nodules surrounding the central necrotic area, and crusting papules and nodules around the head and neck (). Buprenorphine was administered (Vetergesic [Ceva] 20 μg/kg IV q8h) to provide analgesia.
The following day, 7 days after initial presentation, biopsies of the affected areas were taken. Biopsies from the head and ventral lesions identified locally extensive ulceration, covered with a thick layer of necrotic tissue. There was also extensive epidermal and adnexal necrosis with follicular and epidermal keratinocytes containing large, eosinophilic intracytoplasmic inclusion bodies, consistent with viral inclusion bodies. Bacteriology swabs taken from the lesions did not yield any bacterial growth.
Thoracic radiographs were unremarkable, with no evidence of pulmonary changes. Prior to biopsy results being obtained, a presumptive diagnosis of poxvirus was made and treatment with intravenous rFeIFN-ω (Virbagen Omega [Virbac] 1MU/kg SC q24h for 3 days) was commenced.
On day 9, some improvement had been seen in the cat’s demeanour with a return of appetite. The lesions affecting the head had not progressed and no new lesions were noted. The central necrotic region remained static, with the subcutaneous swelling becoming softer on palpation. The cat was discharged later that day; the owner was informed of the zoonotic potential and appropriate measures to take.
The cat re-presented on day 12, with its appetite having reduced, resulting in difficulty administering oral medications. The cat was lethargic again. The cat was given intravenous rFeIFN-ω (as above) for a further 3 days. However, by day 14, de novo nodular lesions had developed on the neck, head and thoracic limbs. The ventrally necrotic region began expanding in size and the small raised papules were becoming more evident again. FeLV and FIV status were confirmed as negative, using a bidirectional flow ELISA Snap test.
The following day, the cat became progressively obtunded and developed anisocoria. Given the limited response to treatment, and progression of clinical signs with CNS involvement, the owners elected for euthanasia.
A necropsy was performed at the Royal (Dick) School of Veterinary Studies. The eschar lesion was found to extend full thickness through the dermis (). Quantitative PCR for CPxV was performed on this tissue, with high amounts of viral DNA identified. Histopathology of this lesion identified a complete loss of the epidermis, and expansion of the dermis with an inflammatory infiltrate dominated by macrophages, neutrophils (mature and degenerate) and occasional lymphocytes. There were extensive areas of cell necrosis with well-demarcated, eosinophilic, intracytoplasmic inclusion bodies (). The post-mortem examination also showed multifocal to coalescing, raised, alopecic and erythematous lesions affecting all four limbs. The lungs had multifocal areas of consolidation, with small quantities of white foam within the terminal bronchi. The pericardium was thickened with a moderately increased amount of pericardial fluid. As neurological changes were evident clinically, histopathology of the cerebral hemispheres and cerebellum was performed. There was marked microgliosis of all areas, with many having abundant cytoplasm within them. Occasionally eosinophilic intracytoplasmic inclusion bodies were identified ().
The findings were consistent with multi-systemic disease with terminal neurological involvement, which has not been reported previously with CPxV infection.


An apparently healthy 2-year-old female child brought to us with a history of noisy breathing, with no history of cold, cough, choking spell, or difficulty in swallowing or drooling of saliva, since morning. On examination, the child was irritable with audible stridor and no cyanosis. Her pulse rate was 112/min, respiratory rate of 48/min, blood pressure 84/60 mmHg, and SpO2 of 76% on room air. On examination, trachea was central, suprasternal and sub coastal retractions were present. On auscultation, the child had bilateral equal air entry with bilateral conducted sounds. Other systems were normal. Chest X-ray revealed prominent bronchovascular markings with no direct or indirect evidence of FB []. In view of inspiratory stridor and child's worsening clinical parameters, suspicion of FB aspiration was raised. Hence, the child was subjected to rigid bronchoscopy, which revealed minimal purulent material in the trachea with no evidence of FB. However, child persisted to have respiratory symptoms post bronchoscopy and required ventilatory support for few days. We noticed drooling of saliva when the child was on ventilator; hence, computed tomography (CT) scan thorax was done which surprisingly revealed radiopaque linear FB posterior to cricopharynx [Figure and ]. Flexible esophagoscopy revealed tear in the cricopharynx with metallic FB posterior to cricopharynx. The child was subjected to thoracoscopy at the same time, which revealed the sharp metallic FB, the metallic foil posterior to cricopharynx with tear in esophageal wall. Thoracoscopic removal of metallic sharp FB was done successfully []. However, unfortunately, postoperatively, the patient could not be revived due to widespread sepsis.


A 48-year-old male presented with complaints of exertional breathlessness, pain in and around the neck region, dry cough sometimes, and increased frequency of the stool passage (7–8 times/day) approached critical care outpatient department. The pain was described as dull ache stretch type of feeling. He also described the feeling of tiredness throughout the day. The patient had a history of 5 years pulmonary tuberculosis, nondiabetic, nonasthmatic with no history of any exposure to environmental pollutants and no any relevant surgical history. His personal history depicted him as a smoker, nonalcoholic, with loss of appetite, no weight loss and had normal sleep. No significant family history was present.
He underwent multiple investigations such as X-rays and contrast-enhanced computed tomography and revealed dense areas of fibrosis affecting the right and left upper lobes with calcified mediastinal lymph nodes. The patient was referred by the chest physician to the Physiotherapy Department for the complaint of pain in and around the neck region. The patient had been treated by antitubercular drugs in the past. At present, he has been prescribed bronchodilators and nonsteroidal anti-inflammatory medications. No other treatment options were found to relieve his symptoms.
On presentation, his blood pressure was 134/86, pulse was 82 beats/min, and he was weighing 70 kg. His nasal cavity showed no deviated nasal septum, no polyp, and no sinus tenderness; throat and oral cavity examinations did not show any congestion or tonsillar enlargement. Percussion revealed impaired resonance in the supraclavicular areas more on the right side. Auscultation revealed decreased breath sounds and fine crepitations. He scored 3 on a patient-reported modified Medical Research Council (mMRC) dyspnea scale.
Against the background of overall diagnosis the osteopathic findings found were reduced lung motility on the right side, sphincter-like areas of tightness and tenderness, supraclavicular region tightness more on right than left side, base of occiput restriction, and increased peristalsis. The remaining assessment was normal.
The OMT techniques were chosen for their effectiveness in addressing pulmonary dysfunction. The techniques chosen were all major diaphragms’ release [], sacral release, occipitoatlantal release [], sphincter-like areas’ release, PF release [], pulmonary balance, pleurovertebral ligament release [], mid-cervical [], posterior aponeurosis release [], pelvic diaphragm release [], thoracic outlet release [], hyoid diaphragm release [], and first rib muscle energy technique. The plan was made for 2 sessions/week for 4 weeks. On the following consultation, it was found that the patient got relief from the individual symptoms, mMRC was decreased from 3 to 1, and the overall improvement in 13-item shortness of breath with daily activities (13iSOBDA). The changes in 13iSOBDA and mMRC at the end of each week of intervention (WoI) are displayed in . The follow-up to see the retention of improvement in the patient was not possible as he was not available further 4 WoI due to inevitable circumstances at the critical care outpatient department.


A 77-year-old right-handed man was admitted to our department with recurrent episodes of transient amnesia. The patient had no other notable past medical or psychiatric disease. Two days before admission, the patient experienced an episode of transient amnesia that began abruptly during breakfast. He could not remember his job and kept asking why he had to go to work despite his wife’s repeated explanations. The symptoms lasted for about 10 minutes and then disappeared. Similar symptoms were observed again on the next day. The patient did not remember his nephew’s wedding, which had taken place 4 days prior. He continued to ask when the nephew was married and why he was married so early. The patient’s memories gradually returned over a period of 20 minutes. After these episodes, however, the patient remembered what happened during those events. During the above episodes, the patient’s family did not observe any other cognitive dysfunction other than amnesia. The patient was alert, fluent, and not disoriented to place or person.
Routine physical and neurological examination revealed no abnormalities. The patient had a score of 29 on the Korean version of the mini-mental examination (K-MMSE) (2 out of 3 on memory recall test, could recall the other when cued). Magnetic resonance imaging (MRI) and MR angiography revealed no abnormalities in the hippocampi or other structures related to memory. On electroencephalographic (EEG), epileptiform discharges were observed in the right temporal leads, including F8 and T2 (). Brain single-photon emission computed tomography revealed no significant increase or decrease of perfusion in the temporal lobes. Routine blood tests, including blood cell counts, routine chemistry tests, and tests to determine the levels of ammonia and creatine phosphokinase revealed no significant abnormalities. The patient was treated with 15 mg/kg of carbamazepine controlled-release (CR), followed by maintenance dose of 200 mg twice per day. He has been free of memory disturbances for 3 months.


A 63-year-old right-handed woman was admitted for evaluation of recurrent and brief memory disturbances. Her husband noticed that the patient suffered from retrograde amnesia upon waking. Specifically, the patient repeatedly asked about what she did last night. The amnesia lasted for about thirty minutes. During these attacks, cognitive functions other than memory seemed to remain intact. One month later, when the patient exited the subway train, she lost her way for about 10 minutes. The patient remembered these amnesic episodes and what she did during those events.
Routine physical and neurological examination revealed no abnormalities. The patient had a score of 24 on the K-MMSE (1 out of 5 on the attenuation and concentration test and 1 out of 3 on the memory recall test, could recall the others when cued). The patient did not show significant declines in cognitive functions and activities of daily living observed by her family. Brain MRI, MR angiogram, and EEG revealed no abnormalities. Routine blood tests also revealed no abnormalities. The patient was treated with 300 mg of valproic acid twice per day. She had not been taking any medicine about cognitive dysfunction before and after those tests. Her symptoms did not recur for 3 years.
However, she developed transient repeated amnesia after the symptom-free interval. Diffusion-weighted MRI and blood tests revealed no abnormalities, but intermittent rhythmic high-voltage sharp waves were observed in the right temporal area (). After the addition of 100 mg zonisamide to her medication, the patient has been symptom-free for 1 month.


A 62-year-old woman was referred to our outpatient clinic in February 2013, after visiting two different neurologists in 2012 who diagnosed her with CD, followed by an unsuccessful treatment episode in a rehabilitation clinic. The patient reported the following progressive problems since 2009: loss of power in the left arm and leg, and problems keeping her balance, sometimes resulting in a drunken gait and falling. In the 4 years before referral to our clinic, the patient had fallen spontaneously five times, without losing consciousness and with the ability to stand up immediately afterward. Furthermore, double vision occurred during fatigue, and the patient had difficulty articulating, difficulty finding words, pain in almost all joints and muscles, poor memory function, and difficulty in concentration due to which she could no longer read or solve puzzles – her favorite pastime. As a result, the patient experienced sleeping problems, low mood, no desire to perform activities, and a passive death wish.
In 2014, the patient again visited the neurological outpatient department. Anamnesis revealed progressive difficulties with speech and swallowing as well as falls due to balance disorder since 2009. On neurological examination, we saw a patient with a surprised look. Dysarthria was present, as well as a vertical upward supranuclear gaze palsy and slowing of downward vertical saccades. There was a prominent postural instability and a positive pull test. Snout reflexes were present. A left-sided striatal toe was seen. Rigidity and bradykinesia were present in legs more than arms. The applause sign was positive. Neither apraxia nor cortical sensory deficit was found, nor was there dysmetria or evidence of autonomic failure. Together with evidence of mesencephalon atrophy on MRI of the cerebrum and results on cognitive testing (described further), we concluded that the patient fulfilled the National Institute for Neurological Disorders and Stroke and Society for PSP criteria (NINDS-SPSP) criteria for probable PSPS.