The extrapyramidal syndromes of chronic kidney disease and dialysis (EPS-CKDD): diagnostic criteria, risk factors and prognosis.

BACKGROUND: Acute extrapyramidal movement disorders in dialysis patients are rare, inconsistently defined and have uncertain aetiology and prognosis. AIM: Define diagnostic criteria, prognosis and risk factors. DESIGN AND METHODS: Retrospective case series review of 20 patients (14 female, mean age 62 years) receiving dialysis for a median of 15 (interquartile range 4-35) months who presented with acute parkinsonism (AP = 11) or chorea/athetosis (CA = 9). RESULTS: All patients had type 2 diabetes (HbA1c 6.8 ± 1.0) and had received metformin. Lactic acidosis was present in 2 patients at presentation and serum lactate was elevated in 7/15 patients tested. No patient had abnormal copper or thyroid metabolism and 5/8 patients tested returned marginal abnormalities in heavy metal screening. Magnetic resonance imaging (MRI) revealed characteristic bilateral symmetric T2 hyperintensity of the basal ganglia (BG), predominantly putamen and globus pallidus (the lentiform nucleus) and more extensive involvement of the external and internal capsules in patients with AP presentation. Post-mortem demonstrated cytotoxic necrosis of the BG. Therapy included thiamine, intensive dialysis and cessation of metformin. Two patients died acutely, nine recovered and nine had residual symptoms. Median survival did not differ by presentation: AP 24 [95% confidence interval (CI) 21-27] and CA 33 (95% CI 32-35) months, P = 0.21. CONCLUSIONS: There are two distinct clinical extrapyramidal movement disorders associated with specific diagnostic MRI imaging that support the diagnosis of the extrapyramidal syndromes of chronic kidney disease and dialysis. The associations with diabetes, metformin and metabolic acidosis suggest a common pathogenic mechanism but require additional study. Early recognition and treatment may improve outcomes.

Fulminant Anti-GAD antibody encephalitis presenting with status epilepticus requiring aggressive immunosuppression.

Antibodies against glutamic acid decarboxylase (GAD) are reported in association with numerous neurological conditions including temporal lobe epilepsy and limbic encephalitis. We report a case of Anti-GAD-Antibody associated encephalitis presenting with epilepsia partialis continua (EPC) progressing to a fulminant encephalopathy preferentially affecting the frontal lobes associated with coma and refractory status epilepticus. The abnormalities identified on MRI included marked bilateral frontal lobe involvement which has not been reported in other auto-immune encephalitides and may be specific for Anti-GAD-Antibody associated encephalitis. Similar to the majority of cases of Anti-GAD associated neurological disturbance no underlying malignancy was identified. Treatment with high dose corticosteriods, IVIG and plasmapheresis had minimal response, but escalation of treatment with rituximab and cyclophosphamide was associated with clinical improvement, reducing antibody titers and resolution of MRI changes.

Ischemic diffusion lesion reversal is uncommon and rarely alters perfusion-diffusion mismatch.

OBJECTIVE: The use of diffusion-weighted imaging (DWI) to define irreversibly damaged infarct core is challenged by data suggesting potential partial reversal of DWI abnormalities. However, previous studies have not considered infarct involution. We investigated the prevalence of DWI lesion reversal in the EPITHET Trial. METHODS: EPITHET randomized patients 3-6 hours from onset of acute ischemic stroke to tissue plasminogen activator (tPA) or placebo. Pretreatment DWI and day 90 T2-weighted images were coregistered. Apparent reversal of the acute ischemic lesion was defined as DWI lesion not incorporated into the final infarct. Voxels of CSF at follow-up were subtracted from regions of apparent DWI lesion reversal to adjust for infarct atrophy. All cases were visually cross-checked to exclude volume loss and coregistration inaccuracies. RESULTS: In 60 patients, apparent reversal involved a median 46% of the baseline DWI lesion (median volume 4.9 mL, interquartile range 2.6-9.5 mL) and was associated with less severe baseline hypoperfusion (p < 0.001). Apparent reversal was increased by reperfusion, regardless of the severity of baseline hypoperfusion (p = 0.02). However, the median volume of apparent reversal was reduced by 45% when CSF voxels were subtracted (2.7 mL, interquartile range 1.6-6.2 mL, p < 0.001). Perfusion-diffusion mismatch classification only rarely altered after adjusting the baseline DWI volume for apparent reversal. Visual comparison of acute DWI to subacute DWI or day 90 T2 identified minor regions of true DWI lesion reversal in only 6 of 93 patients. CONCLUSIONS: True DWI lesion reversal is uncommon in ischemic stroke patients. The volume of apparent lesion reversal is small and would rarely affect treatment decisions based on perfusion-diffusion mismatch.

Disseminated necrotizing leukoencephalopathy following low-dose oral methotrexate.

Leukoencephalopathy is a recognized complication with intrathecal or intravenous methotrexate (MTX). We report a 59-year-old lady who developed MTX leukoencephalopathy with long-term low-dose oral MTX. She developed posterior leukoencephalopathy (PLE) that initially was reversible on discontinuation of oral MTX. Four months later, she developed disseminated necrotizing leukoencephalopathy (DNL), and was left with devastating neurological deficits. The sequential conventional magnetic resonance imaging (MRI), diffusion weighted imaging (DWI), MR perfusion (MRP) and MR spectroscopic (MRS) changes are highlighted in this report. MRP and MRS showed more wide spread abnormalities than DWI. Stereotactic biopsy from the lesion revealed demyelination with macrophagic infiltration, pericapillary lymphomononuclear aggregation, fibrinoid changes in the capillaries and neovascularization. Of the two cases of PLE with oral MTX reported in literature, one reversed clinically and radiologically with the discontinuation of MTX. To the best of our knowledge, this is the first reported case of DNL following oral MTX in the world literature.

Non-convulsive status epilepticus: a rare presentation of juvenile myoclonic epilepsy.

We present a case of a boy with juvenile myoclonic epilepsy (JME) who presented with features of non-convulsive status epilepticus (NCSE). This case highlights the fact that NCSE, even though not a common occurrence in JME, should be kept in mind when a patient with previous history of seizures presents with subtle changes in sensorium with no obvious cause.