Atypical acute hemorrhagic leukoencephalitis (Hurst's disease) presenting with focal hemorrhagic brainstem lesion.

BACKGROUND: Acute hemorrhagic leukoencephalitis (AHL; Hurst's disease) is a rare, severe, inflammatory CNS disease that is typically diffuse, multifocal and associated with petechial hemorrhage. The objective of this study is to report the clinical, radiologic, and pathologic findings in a fatal AHL case with focal brainstem involvement and gross hemorrhage. METHODS: Patient evaluation in a tertiary neurointensive care unit with serial brain magnetic resonance imaging (MRI) and neuropathological examination on autopsy were performed. RESULTS: The patient presented with mild, then rapidly worsening, brainstem impairment to a locked-in syndrome. Brain MRI demonstrated an isolated gadolinium enhancing brainstem lesion that enlarged dramatically over weeks and was associated with gross hemorrhage and necrosis. The patient died despite aggressive treatment with intravenous corticosteroids and plasma exchange. Autopsy demonstrated the isolated severe necrotic lesion consistent with AHL. CONCLUSIONS: AHL may present as a solitary brainstem lesion with gross hemorrhage and should be considered in patients with isolated enhancing brainstem lesions. AHL may be fatal even despite early, aggressive immunomodulatory therapy.

Gait apraxia in multiple sclerosis.

BACKGROUND: Gait apraxia is a gait disorder not attributable to motor, cerebellar, or sensory dysfunction. Gait impairment is common in Multiple Sclerosis (MS), but is mostly attributed to spasticity and ataxia. Impairment ratings scales are designed accordingly and do not separately evaluate apraxia. OBJECTIVE: To describe 15 patients with gait apraxia resulting from MS as their major functional impairment. METHODS: The Mayo Clinic database (1994-2007) was searched for the terms MS and gait apraxia. INCLUSION CRITERIA: Definite MS, significant gait apraxia. EXCLUSION CRITERIA: alternative disorder causing apraxia, predominantly spastic/ataxic gait disorder. RESULTS: 9 (60%) of the patients were women, and 12 (80%) had a progressive MS course. Gait apraxia was evident at a median of 8 years (range 0-34) following MS onset. Median EDSS at recognition of gait apraxia was 6.5 (range 5-8). Cognitive dysfunction was present in 11 (73%) and neurogenic bladder dysfunction in 14 (93%). The commonest MRI findings were confluent periventricular T2 lesions, T1 hypointensity and generalized cerebral atrophy with symmetrical ex vacuo ventricular enlargement. CONCLUSION: Gait apraxia can cause significant functional impairment in MS patients, and may be underrecognized. The natural course of the neurological deficit in such patients is unknown, and may differ from that of MS patients with other ambulatory disabilities.

Acute inflammatory demyelinating optic neuritis: evidence-based visual and neurological considerations.

BACKGROUND: Optic neuritis (ON) is an acute inflammatory demyelinating disorder of the optic nerve that occurs most often in young adults. It can be a monophasic or polyphasic disease isolated to the optic nerve(s) or can be associated with a more widespread demyelinating disorder of the central nervous system such as multiple sclerosis (MS) or neuromyelitis optica. Advances in therapeutics that modify the risk of progression to MS have emphasized accurate diagnosis and risk assessment of patients with ON. REVIEW SUMMARY: ON usually presents with acute unilateral visual loss associated with ocular pain exacerbated by eye movements. Similar to results found in studies assessing corticosteroid used in MS relapses, intravenous methylprednisolone accelerates visual recovery from ON but has no impact on long-term visual outcome. A clinically isolated syndrome (CIS), such as ON, is a clinical demyelinating event that is often the initial attack of relapsing-remitting MS. Disease modifying drugs, in particular interferons-beta, have been shown to reduce the risk of MS conversion in high-risk patients presenting with a CIS. The exact timing and patient selection for the initiation of treatment remain controversial. CONCLUSION: ON is the best studied CIS. The visual prognosis is excellent in most cases regardless of whether the patient is treated with corticosteroids or not. Three recently completed prospective, randomized, double-blinded, placebo-controlled studies have shown that starting a disease-modifying drug at the time of a CIS can reduce the rate of development of MS. However, better diagnostic tools are needed to precisely predict the conversion to MS and the factors influencing disease severity to determine the most appropriate therapeutic paradigm and avoid unnecessary treatment.

Three cases of herpes zoster radiculitis in MS patients treated with natalizumab.

Natalizumab was the first FDA-approved monoclonal antibody for the treatment of multiple sclerosis (MS). We report on 3 natalizumab-treated patients who developed herpes zoster infections. In addition to progressive multifocal leukoencephelopathy, other opportunistic infections have been rarely reported during Natalizumab treatment. We believe that clinicians need heightened awareness of these infections in view of the risks of serious complications.

Relapses and disability accumulation in progressive multiple sclerosis.

OBJECTIVE: We examined the effect of relapses-before and after progression onset-on the rate of postprogression disability accrual in a progressive multiple sclerosis (MS) cohort. METHODS: We studied patients with primary progressive MS (n = 322) and bout-onset progressive MS (BOPMS) including single-attack progressive MS (n = 112) and secondary progressive MS (n = 421). The effect of relapses on time to Expanded Disability Status Scale (EDSS) score of 6 was studied using multivariate Cox regression analysis (sex, age at progression, and immunomodulation modeled as covariates). Kaplan-Meier analysis was performed using EDSS 6 as endpoint. RESULTS: Preprogression relapses (hazard ratio [HR]: 1.63; 95% confidence interval [CI]: 1.34-1.98), postprogression relapses (HR: 1.37; 95% CI: 1.11-1.70), female sex (HR: 1.19; 95% CI: 1.00-1.43), and progression onset after age 50 years (HR: 1.47; 95% CI: 1.21-1.78) were associated with shorter time to EDSS 6. Postprogression relapses occurred in 29.5% of secondary progressive MS, 10.7% of single-attack progressive MS, and 3.1% of primary progressive MS. Most occurred within 5 years (91.6%) after progressive disease onset and/or before age 55 (95.2%). Immunomodulation after onset of progressive disease course (HR: 0.64; 95% CI: 0.52-0.78) seemingly lengthened time to EDSS 6 (for BOPMS with ongoing relapses) when analyzed as a dichotomous variable, but not as a time-dependent variable. CONCLUSIONS: Pre- and postprogression relapses accelerate time to severe disability in progressive MS. Continuing immunomodulation for 5 years after the onset of progressive disease or until 55 years of age may be reasonable to consider in patients with BOPMS who have ongoing relapses.

Poor early relapse recovery affects onset of progressive disease course in multiple sclerosis.

OBJECTIVE: To evaluate the relationship between early relapse recovery and onset of progressive multiple sclerosis (MS). METHODS: We studied a population-based cohort (105 patients with relapsing-remitting MS, 86 with bout-onset progressive MS) and a clinic-based cohort (415 patients with bout-onset progressive MS), excluding patients with primary progressive MS. Bout-onset progressive MS includes patients with single-attack progressive and secondary progressive MS. "Good recovery" (as opposed to "poor recovery") was assigned if the peak deficit of the relapse improved completely or almost completely (patient-reported and examination-confirmed outcome measured ≥6 months post relapse). Impact of initial relapse recovery and first 5-year average relapse recovery on cumulative incidence of progressive MS was studied accounting for patients yet to develop progressive MS in the population-based cohort (Kaplan-Meier analyses). Impact of initial relapse recovery on time to progressive MS onset was also studied in the clinic-based cohort with already-established progressive MS (t test). RESULTS: In the population-based cohort, 153 patients (80.1%) had on average good recovery from first 5-year relapses, whereas 30 patients (15.7%) had on average poor recovery. Half of the good recoverers developed progressive MS by 30.2 years after MS onset, whereas half of the poor recoverers developed progressive MS by 8.3 years after MS onset (p = 0.001). In the clinic-based cohort, good recovery from the first relapse alone was also associated with a delay in progressive disease onset (p < 0.001). A brainstem, cerebellar, or spinal cord syndrome (p = 0.001) or a fulminant relapse (p < 0.0001) was associated with a poor recovery from the initial relapse. CONCLUSIONS: Patients with MS with poor recovery from early relapses will develop progressive disease course earlier than those with good recovery.

A unique presentation of a spinal dural arteriovenous fistula exacerbated by steroids.

Spinal dural arteriovenous fistula (DAVF) is an acquired vascular malformation of the spinal cord that presents as a congestive myelopathy resulting from venous hypertension, edema, and ischemia within the cord. Acute clinical exacerbations have been demonstrated in a variety of clinical settings. We report a unique presentation of a 45-year-old male with progressive paraplegia that acutely worsened following three independent treatments with oral and intravenous steroid administration. Spinal angiogram revealed a spinal DAVF at L3 and the patient underwent successful surgical repair. This report highlights the clinical presentation of spinal DAVF and emphasizes the unique and important potential relationship between steroid administration and clinical deterioration.

A case of metoclopramide-induced oculogyric crisis in a 16-year-old girl with cystic fibrosis.

Oculogyric crisis is a neurologic reaction characterized by bilateral dystonic elevation of visual gaze as well as hyperextension of the neck. This reaction is most commonly explained as an adverse effect of numerous medications, such as dopamine receptor blocking agents or neuroleptic medications and traditional antipsychotic or antiemetic drugs, such as prochlorperazine or metoclopramide. A case of oculogyric crisis induced by metoclopramide is described in this paper.