A 69-year-old Saudi man with diabetes mellitus was admitted to the Neurology Department with an unremitting headache lasting 5 days, episodic confusion, and visual disturbances. According to his family, the headache started gradually over the left side of his head and then became holocephalic and moderate to severe in intensity. The patient reported feelings of nausea and 2 episodes of vomiting. Moreover, his family stated the patient was often seen "bumping" into surrounding objects while ambulating. The patient reported experiencing some visual disturbance during this period. The patient's family felt he appeared confused at times and was not responding to his surroundings. He had no clear history of seizure, according to the family, and his past medical history was unremarkable apart from diabetes. He had sustained a minor head trauma 3 years prior with no concussion; however, his scan was reported to have shown "scattered areas of bleeding" in his brain. He otherwise maintained a healthy life and never required a hospital visit for any medical issues. His family reported the patient had normal cognitive function, especially as someone who ran his own business.
The patient was lethargic upon arrival to the accident and emergency department. Given the apparent risk of airway obstruction, the emergency physician intubated the patient. On general examination, we found no facial phakomas. While the patient was sedated, we found tonic eye deviation with nystagmoid-like eye movement and subtle myoclonic jerks of the distal limb suggestive of subclinical seizures. He was given an intravenous (IV) loading dose of phenytoin in addition to a midazolam infusion. Despite this, he sustained several clinical seizures in the subsequent days. Therefore, he required further titration of midazolam infusion (up to 14 mg/hr) and IV levetiracetam was added to optimize the antiepileptic coverage. His electroencephalogram was obtained postictal. His brain MRI was obtained 1 day following suspected subclinical seizures. Laboratory investigations showed peripehral blood cell count, haemoglobin, renal and liver function within reference range, and his blood glucose was elevated (14.7 mmol/L/264mg/dl).
Moreover, the results of his thyroid function test and his parathyroid hormone and serum vitamin B12 levels were normal. His serum folate level was not available. The screening tests for Hepatitis B antigen, Hepatitis C virus, and human immunodeficiency virus antigens and antibodies were all negative. His anti-TTG immunoglobulin A (IgA) titre was high at 35 U (reference range is up to 20 U), and the screen for antiendomysial antibody was negative, and his anti-Gliadin IgA antibody results were within reference range. Cerebrospinal fluid (CSF) study showed a WBC of 1, red blood cell count of 1, protein level of 36mg/dL, and a glucose level of 7.6mmol/L. The results of the CSF tuberculosis and herpes simplex virus 1 and 2 polymerase chain reaction were negative. We performed a duodenal endoscopic biopsy, but the specimen was not prepared properly; therefore, histopathological examination was suboptimal. We did note, however, increased intraepithelial lymphocytes with normal villous architecture.
The computed tomography (CT) of the patient's brain showed bilateral scattered corticosubcortical parietooccipitotemporal calcification with no oedema or mass effect (Figure 1). The brain MRI with and without contrast showed diffusion-weighted imaging (DWI) restriction over bilateral occipital cortex (more so over the left side) in a gyriform pattern (Figure 2) with concordant area of apparent diffusion coefficient (ADC) hypointensity (Figure 3). Susceptibility weighted magnetic resonance sequences (susceptibility weighted imaging [SWI], susceptibility weighted angiography [SWAN]) demonstrated hyperintensity corresponding to the area of DWI restriction (Figure 5). T1-weighted imaging with contrast showed no contrast uptake (Figure 4), and we saw no oedema or mass effect. We found no cortical atrophy or any deep cerebral vein enlargement. A second brain CT after 1 month (Figure 6) showed no interval change compared to the initial CT and no evidence of residual changes observed in MRI (DWI, ADC, and SWI).
Bilateral cortical calcification has a distinct set of mimickers, and Sturge-Weber syndrome (SWS) is first among the possible differentials. Our patient's brain CT may indeed look identical to SWS. However, it is the constellation of clinical and radiological features that differentiate the two conditions. The important clinically distinguishing feature of SWS is our patient's normal cognition. Psychomotor retardation is seen in 50% of SWS cases, and our patient lacked facial nevus which is prevalent in most SWS cases (except SWS Roach classification type 2). Our patient also had no ocular disease, a presentation found in 77% of SWS cases. Radiologically, SWS has tram line or gyriform-only cortical calcification (and not subcortical, as in our patient). Bilateral calcification (as seen in our patient) occurs in only 25% of SWS patients. Other radiological findings of SWS not seen in our patient are ipsilateral choroid plexus hypertrophy, enlarged transcortical (medullary) veins, ipsilateral cortical atrophy, enlargement of the ipsilateral ventricle, loss of volume of the ipsilateral cranial cavity, and pial enhancing angiomatous malformation (usually ipsilateral to the facial angioma). Therefore, many classic SWS features were not identified in our patient, distinguishing his condition from SWS.
Other conditions known to cause cortical calcification in a similar pattern are, namely, congenital folate malabsorption or the adverse effects associated with methotrexate and antifolate agents. There was no mention of the use of either of these agents. Congenital folate malabsorption would have an associated life-long history of symptoms of malabsorption which is not apparent in our patient. Cortical laminar necrosis could account for such radiological presentation. However, this entity is conventionally thought to be a sequela of a remote traumatic brain injury, anoxic-ischaemic injury, or a metabolic insult that is not present in this patient's past history. Moreover, characteristically, cortical laminar necrosis has T1-weighted gyriform hyperintensity in MRI which was not noted in this patient. Although each of these conditions gives rise to calcified shadows in brain imaging, none are anti-TTG IgA-positive which is specific for the diagnosis of CD.
Antiepileptic treatment with phenytoin and levetiracetam was commenced immediately upon the realisation that the patient has seizures. With the diagnosis of probable CEC, he was started on a strict gluten-free diet.
The patient recovered remarkably and regularly submits to follow-up examinations at our neurology clinic. At his last visit (9 months from his presentation), we found no residual neurological deficit other than mild homonymous hemianopia. Currently, he is fully active, self-sufficient, and has not sustained any seizure for the past 9 months.