Predictors of response to opicinumab in acute optic neuritis.

OBJECTIVE: The objective of this study was to evaluate prespecified and post hoc analyses in RENEW subgroups to identify participants more likely to benefit from opicinumab. METHODS: RENEW assessed the efficacy/safety of opicinumab versus placebo in participants with a first unilateral acute optic neuritis (AON) episode. Difference in visual evoked potential (VEP) latency of the affected eye at 24 weeks versus the fellow eye at baseline was the primary endpoint. Interactions between the primary endpoint and prespecified baseline variables (including age, timing of treatment initiation, and visual impairment) using the median as cut-off were evaluated in the per protocol population using analysis of covariance (ANCOVA); subgroups based on preexisting brain T2 lesion volume were also analyzed. Interactions between the primary endpoint and retinal ganglion cell layer/inner plexiform layer (RGCL/IPL) and retinal nerve fiber layer (RNFL) thickness were assessed post hoc as was weight gain by treatment. RESULTS: Treatment benefit of opicinumab (n = 33) over placebo (n = 36) on the primary endpoint was greatest in participants older than the median age at baseline (≥33 years); the difference versus placebo for baseline age ≥33 years was -14.17 msec [P = 0.01] versus -0.89 msec for baseline age <33 years, [P = 0.87]). Post hoc analysis showed that VEP latency recovery was significantly associated with less RGCL/IPL thinning (P = 0.0164), occurring early on. INTERPRETATION: Age was the strongest prespecified baseline characteristic associated with a treatment effect of opicinumab. A strong association between VEP latency recovery at week 24 and early RGCL/IPL preservation was observed.

Palliative Care in Multiple Sclerosis.

Collaboration between the neurologist and palliative care team in the care of patients with severe demyelinating disease can result in improved patient care, and discussion of the complex ethical issues that arise when a patient expresses a wish to die may be rewarding for both patients and caregivers.

Multiple nocardial abscesses of the brainstem and spinal cord diagnosed after an open biopsy through a cervical partial central corpectomy: case report.

Nocardiosis of the central nervous system is a challenging and difficult diagnosis for the clinician. The combination of infections of the brain and spinal cord is even more rare. The authors report on a patient with multiple lesions in the brainstem and cervical spinal cord. This 81-year-old immunocompetent woman presented with symptoms of progressive walking difficulty and ataxia. The results of an extensive workup with laboratory investigation, MRI, lumbar puncture, positron emission tomography (PET), and bone marrow biopsy remained inconclusive. Only after an open biopsy of a cervical lesion by an anterior approach through a partial central corpectomy of the cervical spine, was the diagnosis of nocardiosis made, allowing for specific antibiotic treatment.

Pseudotumoral rebound of multiple sclerosis in a pregnant patient after stopping natalizumab.

Natalizumab is a highly efficacious treatment for active relapsing-remitting multiple sclerosis, dramatically reducing both clinical and radiological signs of inflammation in most patients. The disease course after stopping treatment and especially the emergence of rebound activity are still a matter of debate. We present a case of dramatic reactivation of clinical disease activity with newly emerging pseudotumoral lesions in a patient who stopped treatment due to pregnancy. Both the clinical and radiological presentation suggest a rebound and necessitate close monitoring of patients stopping their treatment during pregnancy, even after a long period of stable disease.

Anti-glycine receptor antibody mediated progressive encephalomyelitis with rigidity and myoclonus associated with breast cancer.

We describe a 66-year-old woman who presented with a dramatic course of PERM. Anti-glycine receptor antibodies were found. She stabilized after plasma-exchange and partly recovered. Eighteen months later, a diagnosis of smouldering breast cancer with bone marrow metastasis was made. There are indications that this tumor was already present at first presentation. An overview of PERM and anti-glycine receptor antibodies is given.

Toxocariasis presenting as encephalomyelitis.

We describe a farmer who presented with a clinical picture of a transverse thoracic myelitis. MRI showed inflammatory lesions in brain and thoracic spinal cord. Toxocariasis was suspected because of eosinophilia in blood and cerebrospinal fluid, and this diagnosis was confirmed immunologically. He was successfully treated with antihelminthics in combination with corticosteroids. Neurotoxocariasis is rare and diagnosis can be difficult because of the different and atypical clinical manifestations. It should be considered in every case of central neurological syndrome associated with eosinophilia.

MRI with intrathecal gadolinium to detect a CSF leak: a prospective open-label cohort study.

OBJECTIVES: The techniques currently used to detect a cerebrospinal fluid (CSF) leak are an indium radionucleotide scan and a CT scan with intrathecal iodinated contrast agent. They have a low spatial and temporal resolution and are unpleasant for the patient. This open-label prospective observational cohort study was designed to investigate the feasibility, success ratio, complications and therapeutic consequences of MRI with gadolinium administered by lumbar puncture to detect a CSF leak. METHODS: Patients were selected with either confirmed liquorrhoea, recurrent bacterial meningitis, or symptoms, and MRI findings of spontaneous intracranial hypotension. High-resolution T1 weighted MRI with fat suppression of the spinal column at 1 h and of the brain at 6 and 24 h postinjection of 0.5 ml of gadolinium were performed. RESULTS: 27 patients were included. The clinically suspected CSF leak was found in six of eight patients with liquorrhoea, three of five patients with recurrent bacterial meningitis and nine of 14 patients with spontaneous intracranial hypotension. The procedure was easy to perform and generally well tolerated. One patient developed streptococcal meningitis in the hours following the procedure but recovered completely with antibiotic treatment. 17 of 18 patients in whom a dural defect was found underwent surgery. All patients became symptom-free after closure of the dural leak. CONCLUSIONS: Spinal cord and brain MRI after intrathecal gadolinium injection is an easy-to-perform and accurate technique for detection of a dural defect with excellent anatomical detail.

Linezolid-induced inhibition of mitochondrial protein synthesis.

BACKGROUND: Linezolid is an oxazolidinone antibiotic that is increasingly used to treat drug-resistant, gram-positive pathogens. The mechanism of action is inhibition of bacterial protein synthesis. Optic and/or peripheral neuropathy and lactic acidosis are reported side effects, but the underlying pathophysiological mechanism has not been unravelled. METHODS: We studied mitochondrial ultrastructure, mitochondrial respiratory chain enzyme activity, and mitochondrial DNA (mtDNA) in muscle, liver, and kidney samples obtained from a patient who developed optic neuropathy, encephalopathy, skeletal myopathy, lactic acidosis, and renal failure after prolonged use of linezolid. In addition, we evaluated mtDNA, respiratory chain enzyme activity, and protein amount in muscle and liver samples obtained from experimental animals that received linezolid or placebo. RESULTS: In the patient, mitochondrial respiratory chain enzyme activity was decreased in affected tissues, without ultrastructural mitochondrial abnormalities and without mutations or depletion of mtDNA. In the experimental animals, linezolid induced a dose- and time-dependent decrease of the activity of respiratory chain complexes containing mtDNA-encoded subunits and a decreased amount of protein of these complexes, whereas the amount of mtDNA was normal. CONCLUSION: These results provide direct evidence that linezolid inhibits mitochondrial protein synthesis with potentially severe clinical consequences. Prolonged courses of linezolid should be avoided if alternative treatment options are available.