intrathecal chemotherapy combined with systemic chemotherapy has been used for both the prophylactic and therapeutic treatment of hematologic malignancies in the central nervous system . however
, intrathecal chemotherapy has been associated with neurotoxic adverse effects , including myelopathy , encephalopathy , seizure , and cauda equina syndrome .
although myelopathy is the most common adverse effect associated with intrathecal chemotherapy , magnetic resonance imaging ( mri ) has rarely been reported in the literature . here
, we report a case of a 35-year - old female presenting with paraparesis , sensory ataxia , and loss of position sense in her lower limbs after systemic high - dose methotrexate and cytosine arabinoside ( hd - mtx / ara - c ) therapy and intrathecal ara - c therapy .
spinal t2-weighted ( t2-wi ) mri demonstrated abnormal intensity lesions in the dorsolateral column , mimicking subacute combined degeneration ( scd ) .
in addition , we assessed diffusion tensor / kurtosis imaging ( dti / dki ) and q - space imaging ( qsi ) metrics in this myelopathy .
a 35-year - old female underwent partial tumor resection and postoperative steroid therapy for a cerebellopontine angle tumor .
cranial mri revealed a lesion with abnormal intensity in the third ventricle , and transventricular endoscopic biopsy and ventriculostomy were performed .
histological examination revealed the characteristic findings of a diffuse , large b - cell lymphoma .
a course of systemic hd - mtx / ara - c treatment diminished the tumor on brain mri and improved the clinical symptoms .
the patient received an additional 3 courses of hd - mtx / ara - c and repetitive lumbar intrathecal ara - c ( 100 mg ) and dexamethasone ( 4 mg ) .
one month after the first round of intrathecal chemotherapy , the patient complained of bilateral numbness in her lower legs despite normal spinal mri .
she received a repetitive course of intrathecal ara - c ( 40 mg ) and prednisolone ( 4 mg ) with or without intrathecal mtx ( 15 mg ) for 6 months , along with whole - brain radiotherapy for 1 month .
nine months after the first round of intrathecal chemotherapy , the patient gradually developed an unstable gait .
neurological examination revealed a mild lower - limb weakness and a sensory ataxic gait with a positive romberg 's sign .
pinprick , light touch , vibration sensation , and proprioception were impaired below the level of the th10 dermatome .
deep tendon reflexes were normal in all limbs , but diminished abdominal reflexes and bilateral extensor planter responses were noted .
macrocytic anemia was present : red blood cells 2.64  10 l , hemoglobin 9.7 g / dl , mean corpuscular volume 112.5 fl , with a reduced thrombocyte count .
the results of routine biochemistry , autoantibodies , and a thyroid function test were unremarkable .
her serum vitamin b12 level was in the lower limits of normal [ 286 pg / ml ( normal range 180914 ) ] , and her serum levels of folate and copper were slightly reduced [ 2.8 ng / ml ( normal range > 3.1 ) and 65 mg / dl ( normal range 68128 ) , respectively ] .
cerebrospinal fluid ( csf ) studies revealed a white blood cell count of 1/l , a protein level of 24 mg / dl , and increased levels of myelin basic protein ( mbp ; 502 pg / ml ) .
nerve conduction velocities and compound muscle action potentials were normal , while somatosensory evoked potentials demonstrated a normal n 20 latent time ( 19.50 ms ) but prolonged p 40 responses ( 44.1 ms ) .
the patient 's spinal t2-wi mri demonstrated abnormal signal intensity in the bilateral and dorsal columns in the thoracic cord , extending from th3 to th10 ( fig .
we performed dti , dki , and qsi and calculated each parameter ( as described previously [ 2 , 3 , 4 ] ) , in the regions of interest on the dorsal column at th79 and c35 of the patient , along with 4 control subjects .
the results at th79 of the patient and control subjects ( mean  standard deviation ) were as follows : apparent diffusion coefficient ( adc ) ( 10 mm / s ) : 0.55 and 1.16  0.10 ; fractional anisotropy ( fa ) : 0.41 and 0.61  0.14 ; lambda ( 1 ) ( 10 mm / s ) : 0.78 and 2.11  0.19 ; ( 2 + 3)/2 ( 10 mm / s ) : 0.45 and 0.69  0.19 ; full width half maximum ( m ) : 17.45 and 20.32  0.34 ; mean diffusional kurtosis ( mdk ) : 1.65 and 0.85  0.15 .
we also obtained mdk at c35:1.72 , 1.21 , 0.78 and 1.00  0.11 ( fig . 1 , fig .
the disease course , hematological findings , and mri suggested a diagnosis of demyelinating myelopathy due to the combined effect of intrathecal chemotherapy and vitamin and mineral deficiencies .
the patient 's condition did not deteriorate , but also did not improve despite therapy with intravenous administration of vitamin b12 and folic acid .
seventeen months after the first round of chemotherapy , the patient died of recurrent brain lymphoma .
myelopathy has been reported as a significant adverse effect of combination therapy with intrathecal ara - c and systemic hd - mtx [ 5 , 6 ] .
risk factors for the development of intrathecal chemotherapy - related myelopathy include a high - dose and/or frequent exposure to central nervous system - directed therapy . in most patients , paraplegia with bowel and urinary disability is commonly prominent , developing within a few days to several months after intrathecal chemotherapy .
mri findings of intrathecal chemotherapy - related myelopathy include high signal intensity in t2-wi within the central and posterior columns , cord swelling , gadolinium enhancement restricted to the lateral columns , and the features of arachnoiditis .
our patient presented with a slowly developing weakness and an impairment of position sense in the lower limbs during repetitive intrathecal ara - c combined with hd - mtx therapy .
her csf cell count was unremarkable with increased mbp levels , as previously seen in myelopathy due to intrathecal chemotherapy .
conventional mri findings consisted of abnormal signal intensity in the bilateral and dorsal columns in the thoracic cord , extending from th3 to th10 , mimicking scd of the spinal cord
. however , our patient did not present with any other clinical features of scd , such as peripheral neuropathy and dementia .
reported 2 cases of intrathecal mtx - related myelopathy that mimicked the mri findings of scd , as seen in our patient . in both patients ,
described the pathological findings of intrathecal myelopathy as microvacuolization , axonal swelling , and the loss of myelin within the white matter of the spinal cord .
the mechanisms underlying chemotherapy - related myelopathy mimicking scd are still unknown . in a rabbit model ,
intrathecally injected ara - c penetrated the peripheral white matter and geniculate body in the spinal cord , suggesting that ara - c may have toxic demyelinating effects on the dorsolateral columns .
it is well known that although vitamin b12 and folate acid levels are in the lower limits , measuring homocysteine and methylmalonic acid levels can be useful in diagnosing patients with scd who have not received treatment .
we could not confirm homocysteine and methylmalonic acid levels in our patient without vitamin treatment ; therefore , the possibility that a deficiency in several vitamins and minerals may have been associated with the development of scd should be considered in our patient [ 13 , 14 , 15 , 16 ] . furthermore , mtx is a folic acid antagonist and causes chemotherapy - related myelopathy [ 1 , 17 ] .
therefore , a deficiency in vitamins and minerals may have worsened the spinal toxicity of chemotherapy in our patient .
our patient showed a decreased adc and fa at the th79 levels due to markedly decreased 1 , which indicated the preferential restriction of water diffusion along the long tracts such as the corticospinal tract and dorsal column . increased mdk indicated increased microstructural complexity .
these results showed that normal and well - organized white matter structures were damaged predominantly in the long tracts .
the patient also showed an increased or decreased mdk at levels c35 , in spite of the absence of substantial intensity abnormalities on conventional and advanced diffusion mri .
taken together , conventional and advanced mri findings in our patient suggested that cytotoxic demyelination had occurred along the lateral and posterior columns from the lower cervical down to the middle thoracic cord . in conclusion
vitamin and mineral deficiencies may have played a role , in part , in the pathomechanisms of myelopathy in this patient .
spinal diffusion mri revealed cytotoxic demyelination along the posterior columns , which assisted in the diagnosis of demyelinated myelopathy .
our findings suggest that spinal dti , qsi , and dki are useful tools in the diagnosis of chemotherapy - related myelopathy .
 chemotherapy - related myelopathy mimicking subacute combined degeneration ( scd ) has rarely been reported . 
 we encountered a 35-year - old female with sensory ataxia after intrathecal chemotherapy . 
 spinal magnetic resonance imaging showed localized abnormal signal areas in the lateral and dorsal white matter , mimicking scd . 
 diffusion imaging showed restricted water diffusion and increased microstructural complexity , and cerebrospinal fluid analysis showed increased levels of myelin basic proteins , indicating demyelinating myelopathy . 
 advanced diffusion imaging can provide more information on the microstructure of chemotherapy - related myelopathy . 
Introduction
Case Presentation
Discussion
Disclosure Statement