Biotinidase deficiency: A treatable cause of opticospinal syndrome in young adults✰.

Diagnosis of biotinidase deficiency is rare and usually made in infancy, through newborn screening or after presenting symptoms. We present the case of 19-year old male with progressive optic atrophy and in a second phase spinal cord syndrome unresponsive to immunosuppressive therapies. After diagnosis of profound biotinidase deficiency, oral biotin substitution was started with partial visual improvement and normalization of gait. This case highlights the possibility of late-onset biotinidase deficiency and its treatable character.

Potential benefits of early aggressive immunotherapy in Susac syndrome.

Susac syndrome is a rare vasculopathy of unknown aetiology, affecting prominently young women and electively targeting brain (encephalopathy), retina (visual field defects), and cochlea (hearing loss), of which optimal treatment has yet to be established. We report clinical, CSF and MRI features together with the long-term outcome in a monocentric series of eight consecutive patients with unusual sex ratio (5 male; 3 female), to define the best diagnostic/therapeutic strategy. Six patients presented with the classical clinical triad within less than 6 months after symptoms onset; two did not suffer from sensorineural hearing loss. All but one received a treatment combining high doses of methylprednisolone and cyclophosphamide intravenously. The first two patients had very delayed diagnosis (6-4 months) resulting in severe cognitive sequelae. The third one had only mildly delayed diagnosis (2 months) with subsequent behaviour impairment and severe right hypoacousia. All three were unable to return to work. The last five patients who had early diagnosis and undelayed aggressive treatment were able to resume their professional activities.

Recurrent Miller Fisher syndrome with vestibular involvement.

We describe a patient who had four relapses of Miller Fisher syndrome over a period of 20 years. The classical triad - ophthalmoparesis, ataxia and areflexia - was present during the first two attacks; ataxia was not observed during the third episode. The final recurrence was characterized by signs suggestive of a central involvement of the oculomotor pathways, subclinical slowing of the visual-evoked potentials, and peripheral vestibular hyporeactivity. Brain imaging was normal, but high levels of anti-GQ1b IgG antibodies were detectable during the second relapse and persisted after the fourth recurrence despite complete clinical recovery.

Diagnostic and therapeutic pitfalls in neurosarcoidosis.

Neurosarcoidosis is a diagnostic challenge, especially in the absence of systemic involvement, even when cerebral biopsies show noncaseating granulomas. We report a patient with a pineal germinoma associated with a extensive peri- and intra- tumoural granulomatous reaction, who was first diagnosed as possible neurosarcoïdosis. A second patient was initially considered as suffering from Multiple Sclerosis. Brain biopsy showed typical granulomas and gallium scintigraphy revealed other locations of the disease. Unfortunately, he developed a severe, steroid-induced, epidural lipomatosis at the Th3-Th8 levels and died unexpectedly after surgical decompression. Granulomatous inflammation in a tissue obtained by biopsy from a midline lesion should be always considered for the differential diagnosis of germinoma. Corticosteroid-sparing immunosuppressant drugs should be used early in neurosarcoïdosis.

Anti-alpha-glucose-based glycan IgM antibodies predict relapse activity in multiple sclerosis after the first neurological event.

BACKGROUND: There is no specific serum-based biomarker for the diagnosis or prognosis of relapsing-remitting multiple sclerosis (RRMS). OBJECTIVE: We investigated whether levels of IgM antibodies to Glc(alpha1,4)Glc(alpha) (GAGA4) or to a panel of four glucose-based glycans could differentiate MS from other neurological diseases (OND) or predict risk of early relapse following first presentation (FP) of RRMS. METHODS: Retrospective analysis of 440 sera samples of three cohorts: A) FP-RRMS (n = 44), OND (n = 44); B) FP-RRMS (n = 167), OND (n = 85); and C) FP (n = 100). Anti-GAGA4 IgM levels were measured by enzyme immunoassay in cohort-A and cohort-B. Cohort-C IgM antibodies to glucose-based glycan panel were measured by immunofluorescence. RESULTS: FP-RRMS had higher levels of anti-GAGA4 IgM than OND patients (cohort-A, P = 0.01; cohort-B, P = 0.0001). Sensitivity and specificity were 27% and 97% for cohort-A; and 26% and 90% for cohort-B, respectively. In cohort-C, 58 patients experienced early relapse (<24 months), 31 had late relapse (> or =24 months), and 11 did not experience second attack during follow-up. Kaplan-Meier curves demonstrated decrease in time to next relapse for patients positive for the antibody panel (P = 0.02, log rank). CONCLUSIONS: Serum anti-GAGA4 IgM discerns FP-RRMS patients from OND patients. Higher levels of serum anti-alpha-glucose IgM in FP patients predict imminent early relapse.

Poliomyelitis-like syndrome with matching magnetic resonance features in a case of Lyme neuroborreliosis.

Lyme disease is a multisystemic disorder caused by an epizootic organism of the spirochete group, called Borrelia burgdorferi, which is transmitted to humans by ticks of the genus Ixodes. Lyme neuroborreliosis may occur during the early dissemination phase, most often as a painful meningo-radiculitis and very rarely as a radiculo-myelitis, whereas encephalomyelitis is observed in the late phase. We report the case of a patient with an early subacute poliomyelitis-like syndrome closely matching the selective involvement of the anterior horns and roots of the cervical spinal cord seen on magnetic resonance imaging. This condition improved with appropriate antibiotics.

Poliomyelitis-like syndrome with matching magnetic resonance features in a case of Lyme neuroborreliosis.

Lyme disease is a multisystemic disorder caused by an epizootic organism of the spirochete group, called Borrelia burgdorferi (Bb), which is transmitted to humans by ticks of the genus Ixodes. Lyme neuroborreliosis may occur during the early dissemination phase, most often as a painful meningo-radiculitis and very rarely as a radiculo-myelitis, whereas encephalomyelitis is observed in the late phase. We report the case of a patient with an early subacute poliomyelitis-like syndrome closely matching the selective involvement of the anterior horns and roots of the cervical spinal cord seen on magnetic resonance (MR) imaging. This condition improved with appropriate antibiotics.

Mitoxantrone-related acute leukemia in two MS patients.

We report two new cases of mitoxantrone-related leukemia occurring in two patients with multiple sclerosis (MS), 14 and 18 months after the last infusion of the drug. One patient was successfully treated. We were able to collect 29 other cases in the literature. Most of them were single reports but some were described within cohorts of mitoxantrone-treated MS patients. The incidence rate was 0.65% from all cohorts totalizing 2299 patients. Acute promyelocytic leukemia with the translocation t(15;17) was over-represented in the MS population in comparison with cancer patients also treated with mitoxanrone. The occurrence of leukemia was dose-independent and appeared with a mean delay of 20 months after the end of the treatment.

Acute ischaemic pontine stroke revealing lyme neuroborreliosis in a young adult.

We report the case of a 23-year-old male patient who suddenly developed right hemiparesis, cerebellar ataxia, dysarthria, and bilateral dysmetria. Brain magnetic resonance (MR) examination demonstrated hyperacute ischaemic lesions within the pons. CSF analysis revealed a high protein content, lymphocytic pleocytosis, and oligoclonal IgG bands not present in the serum. Elevated IgM and IgG anti-Borrelia burgdorferi antibodies were shown in both serum and CSF samples, associated with an intrathecal synthesis of these antibodies. Ischaemic CNS lesions have been rarely observed as the first manifestation of Lyme neuroborreliosis. The putative mechanism for parenchymal ischaemia is the local extension of inflammatory changes from meninges to the wall of penetrating arterioles.

Polymerase chain reaction analysis and oligoclonal antibody in the cerebrospinal fluid from 34 patients with varicella-zoster virus infection of the nervous system.

OBJECTIVE: To study cerebrospinal fluid (CSF) and serum samples from 34 consecutive patients suspected of having varicella-zoster virus (VZV) infection of the central nervous system (CNS). POPULATION AND METHODS: The patients were divided into three groups. The first group consisted of 27 patients with a rash in one to three dermatomes and clinical suspicion of meningitis and radiculitis; among them, three subgroups were distinguished according to the affected dermatome: ophthalmicus (n = 9), oticus (n = 11) and cervico-thoraco-lumbar zoster (n = 7). Four cases of zoster sine herpete (ZSH) were included in the second group: these patients presented with either radiculitis (n = 2) or meningoencephalitis (n = 2), without cutaneous eruption. The third group consisted of three patients with a generalised rash and encephalitis. A polymerase chain reaction (PCR) for VZV DNA and antigen-driven immunoblots for oligoclonal anti-VZV antibodies were carried out on all CSF samples. RESULTS: PCR of the CSF was positive in 44% of the patients from the first group, mainly within the first 7 days after eruption. In addition, intrathecal synthesis of anti-VZV antibodies was detected in 37% of patients, always after an interval of 7 days (p<0.0001). Among the four patients with ZSH, a positive VZV PCR was detected in three patients and CSF-specific oligoclonal anti-VZV antibodies in two. PCR was also positive in the CSF of two of the three patients with generalised rash and encephalitis; local production of anti-VZV antibodies was seen in a second CSF sample in one patient, and was also present in the third patient. CONCLUSION: Amplification of VZV DNA by PCR in the CSF and antigen-driven immunoblots have important diagnostic value in suspected VZV infection, although their presence depends on the timing of the CSF sampling. VZV is thought to be a causative agent in unexplained cases of meningitis associated with radiculitis or focal CNS symptoms, even in the absence of skin manifestations. In such patients, rapid diagnosis by this combined approach permits early antiviral treatment.

L-2-Hydroxyglutaric aciduria: clinical, genetic, and brain MRI characteristics in two adult sisters.

L-2-Hydroxyglutaric (L-2-HG) aciduria is a rare inherited metabolic disease usually observed in children. Patients present a very slowly progressive deterioration with cerebellar ataxia, mild or severe mental retardation, and various other clinical signs including extrapyramidal and pyramidal symptoms, and seizures. The disease is characterized by increased levels of L-2-HG in body fluids such as urine and cerebrospinal fluid. We report on two sisters from consanguineous parents, in whom L-2-HG aciduria was diagnosed at an adult age. Although magnetic resonance imaging and spectroscopic findings were severely abnormal in both, they experienced a different clinical course. The older sister presented with severe mental retardation, recurrent epileptic seizures, and progressive deterioration in her ability to walk and to talk; she is now confined to a wheelchair with severe speech deficit. In contrast, the younger sister only had a few epileptic seizures in childhood and moderate mental retardation, is still able to walk, and performs manual work, and has a social life in a specialized institution for moderately mentally handicapped persons. For the two patients, a complete deletion of exon 9 was demonstrated in a gene located on chromosome 14q22.1, which most probably encodes for L-2-hydroxyglutarate dehydrogenase. The pathological findings observed in this metabolic disorder could therefore be related to a toxic effect of L-2-hydroxyglutarate on the central nervous system, although the presence of other toxic metabolites cannot be excluded.

Paraneoplastic rhombencephalitis and brachial plexopathy in two cases of amphiphysin auto-immunity.

Amphiphysin, a synaptic vesicle protein, is an auto-immune target in rare cases of paraneoplastic neurological disorders. We report two additional cases with distinct neurological syndromes and paraneoplastic anti-amphiphysin antibodies. The first patient, a 59-year-old man, presented with cerebellar and cranial nerve dysfunction and small cell lung carcinoma. The second, a 77-year- old woman, presented with left brachial plexopathy followed by sensorimotor neuropathy and breast carcinoma.

Clinical, electrophysiological and brain imaging features during recurrent ictal cortical blindness associated with chronic liver failure.

Transient neuroimaging features indicating primary cortical and secondary subcortical white matter cytotoxic oedema have been described in association with prolonged or intense seizures. We describe the unusual condition of recurrent ictal cortical blindness due to focal occipital status epilepticus, in the context of chronic hepatic failure. There was a close association between the onset and disappearance of clinical, electrophysiological and magnetic resonance imaging abnormalities.

Long-term follow up of glatiramer acetate compassionate use in Belgium.

Between June 1995 and November 1998, 228 patients with relapsing-remitting Multiple Sclerosis started treatment with glatiramer acetate (Copaxone) 20 mg once daily in the frame of a "compassionate use" protocol in 15 Belgian centers. Following an average treatment period of 5.8 years, treating neurologists were requested to fill in follow-up forms indicating neurological disability status and side effects during the previous 6 months. These data were available for 134 patients. In this group, the Expanded Disability Status Scale (EDSS) improved in 26.3% of patients. An additional 36.8% of patients remained neurologically stable. The Ambulation Index (AI) showed similar results: 12.5% of patients improved, 50% of patients remained stable, and 37.5% worsened. Only 10% of patients dropped out due to several reasons. The adverse events occurring in the period preceding the follow-up survey were non-serious and consistent with the current product information of glatiramer acetate. Among the 94 patients no longer followed-up in the compassionate program, reasons for lost to follow-up were obtained for 63; most of them (41) had stopped GA treatment or switched to another disease-modifying treatment. Overall these results are very similar to the ones reported in the extension study of the pivotal trial (Johnson et al., 2000), and indicate that patients treated with glatiramer acetate have a better outcome than expected on the basis of the natural course of the disease. Despite limitations of the study design, this report confirms the sustained efficacy of glatiramer acetate in reducing the disease progression in patients with relapsing-remitting multiple sclerosis treated in day-to-day clinical practice.

Paucisymptomatic brainstem lesions revealing CNS schistosomiasis.

We describe clinical and magnetic resonance (MR) features in a 69-year-old, Caucasian woman presenting with an unusual meningeal onset of cerebral schistosomiasis. Magnetic resonance work-up demonstrated supra- and infratentorial lesions with prominent brainstem involvement contrasting with the paucisymptomatic clinical presentation. Because of a recent stay in Uganda, including swimming in Lake Victoria, a diagnosis of neuroschistosomiasis was suggested. Serological tests and rectal biopsy confirmed the putative diagnosis. The patient was successfully treated with praziquantel at a dose of 50 mg/kg/day for 15 days. Brain MRI abnormalities improved dramatically within two months.

Paraneoplastic limbic encephalitis: diagnostic relevance of CSF analysis and total body PET scanning.

We report two cases of paraneoplastic limbic encephalitis (PLE) that differed in their clinical patterns, the underlying tumours, and the associated paraneoplastic antibodies. The first patient was a young adult male, with anti-MA-2 antibodies and testicular tumour. The clinical picture was restricted to limbic involvement. The second patient was a 56-year old, female heavy smoker; with seizures and depression, but also vertigo and diplopia. A low level of serum anti-Hu antibodies led to the detection of a small cell lung carcinoma by total body PET-scanning. In both cases, intrathecal synthesis of CSF oligoclonal IgG bands and of the corresponding paraneoplastic antibodies was demonstrated.

[Chorea-athetosis in the anti-Hu syndrome]. / Mouvements choréo-athétosiques et syndrome anti-Hu.

INTRODUCTION: Paraneoplastic choreo-athetoses are rare. We report a case of anti-Hu syndrome with choreo-athetosis. CASE REPORT: A 48-year-old woman developed a small-cell lung carcinoma revealed by an anti-Hu syndrome. The neurological features included choreo-athetosis predominating in the upper limbs, chronic sensorimotor axonal polyneuropathy, and opsoclonus. The cerebrospinal fluid was acellular and contained several oligoclonal IgG bands, not found in the corresponding serum. Magnetic resonance imaging revealed bilateral high-intensity lesions on T2/FLAIR sequence in the corona radiata. Moderate transitory improvement of the paraneoplastic neurological syndrome was observed after several carboplatin-etoposid cycles. CONCLUSION: A paraneoplastic origin must be considered in all cases of unexplained choreo-athetosis. Paraneoplastic choreo-athetosis is most often associated with other neurological symptoms. The most frequent associated tumor is a small-cell lung carcinoma with anti-CRMP5 and/or anti-Hu antibodies. Our patient developed paraneoplastic choreo-athetosis related to an anti-Hu syndrome in the absence of anti-CRMP5/CV2 antibodies. Paraneoplastic choreo-athetosis might result from a central lesion, and/or from proprioceptive deafferentation subsequent to peripheral neuropathy.