Jean-Claude Hache

Devic's neuromyelitis optica: clinical, laboratory, MRI and outcome profile

Devics neuromyelitis optica (NMO) associates optic neuritis and myelitis without any other neurological signs. Many patients with NMO may be diagnosed as having multiple sclerosis (MS), optic neuritis and myelitis being the inaugural symptom in 20% and 5% of MS cases, respectively. The aim of our study was to compare a new NMO cohort with recent studies and to try to determine the place of NMO in the spectrum of MS. We retrospectively studied 13 patients with a complete diagnostic workup for NMO. We compared our data with the most recent studies on NMO and with the criteria proposed by Wingerchuck et al. [Neurology 53 (1999) 1107]. We also determined whether these patients fulfilled the diagnostic criteria for MS. Thirteen patients (10 women and three men, with a mean age of 37.4 years) were included in the study. We found similar results to previously published data, except for an association with vasculitis in 38% of our cases. All but three of the patients fulfilled the clinical criteria for MS and two patients fulfilled both clinical and MRI criteria for MS. However, if we applied more restrictive criteria concerning spinal cord and brain MRI and CSF, none of our NMO patients fulfilled the MS diagnostic criteria. NMO might therefore be differentiated from MS by the application of more stringent criteria. Furthermore, all NMO patients should be investigated for vasculitis, even those with no history of systemic disease.

Outer retinal dysfunction in patients treated with vigabatrin

OBJECTIVE To assess early visual impairment related to vigabatrin prospectively in patients with and without visual symptoms. BACKGROUND Vigabatrin acts as an inhibitor of gamma-aminobutyric acid (GABA) transaminase. GABA-induced ion transport changes in the retinal pigment epithelium have been described. The electro-oculogram (EOG) is a clinical test that reflects photoreceptor and pigment epithelium function. PATIENTS AND METHODS Of the 22 consecutive patients presenting with a history of partial seizures currently treated with vigabatrin, 20 were included in the study. A complete clinical ophthalmologic and neurologic examination was performed, including static 100-point perimetry, EOG, and electroretinogram (ERG). RESULTS In 14 of 20 patients, the light/dark ratio (Arden ratio) of the standard EOG was reduced in at least one eye. The a- and b-wave amplitudes and implicit time of the ERG were within the normal range in all patients; however, ERG oscillatory potentials could not be recorded in 10 patients. Twelve patients had visual field constriction; five complained of visual symptoms. The most severe visual impairment was observed in patients treated with both vigabatrin and valproate. CONCLUSIONS There is some evidence of outer retinal dysfunction in the patients treated with vigabatrin. EOG, a more sensitive diagnostic tool than ERG for screening vigabatrin-treated patients, also appears to be more specific.

Autonomic and respiratory dysfunction in Charcot–Marie–Tooth disease due to Thr124Met mutation in the myelin protein zero gene

OBJECTIVE To report the clinical and electrophysiological characteristics of a family presenting Charcot-Marie-Tooth disease (CMT) associated with autonomic nervous system disturbances. METHODS We studied nerve conduction values, postural adaptation, sympathetic skin reflex, the variation in heart rate by the Valsalva ratio and pupillometry in 7 members of a French family in which CMT due to a Thr124Met mutation in the myelin protein zero (MPZ) gene was diagnosed. RESULTS Clinical and laboratory evidence of autonomic nervous system disturbances were found in the affected individuals. The clinical phenotype was characterized by sensorimotor peripheral neuropathy, defined as axonal type by electrophysiological studies, and was associated with severe pain, bladder dysfunction, sudorimotor disturbances and abolished pupillary reflex to light. Moreover, two patients had severe restrictive respiratory insufficiency requiring noninvasive mechanical ventilation. CONCLUSIONS Our study demonstrates that autonomic disturbances may be one of the major clinical signs associated with CMT secondary to MPZ gene mutation in codon 124. Testing of pupillary reflex allows the discrimination of affected and unaffected subjects in our family. However, involvement of the autonomic nervous system in this type of neuropathy is unclear and further studies are required to elucidate the role of the MPZ gene in the autonomic nervous system.

Visual evoked potentials study in chronic idiopathic inflammatory demyelinating polyneuropathy

BACKGROUND The frequency of the association between chronic demyelinating inflammatory polyneuropathy (CIDP) and central nervous system (CNS) demyelinating lesions is probably underestimated. OBJECTIVE To investigate the occurrence of combined central and peripheral demyelination in CIDP patients and to correlate visual evoked potential (VEP) abnormalities with CNS demyelinating lesions, observed on brain magnetic resonance imaging, and antibodies against glycolipids. METHODS Nerve conduction studies, brain MRI and antibodies against glycolipids were prospectively studied in 17 patients who fulfilled the diagnostic criteria proposed for CIDP (Cornblath DR, Asbury AK, Albers JW, Feasby TE, Hahn AF, McLeod JG, Mendell JR, Parry GJ, Pollard JD, Thomas PK. Ad Hoc Subcommittee of the American Academy of Neurology AIDS Task Force. Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy. Neurology, 1991;41:617-618). VEPs were performed in each case before and after 6 months treatment with either intravenous immunoglobulins (IVIG) or steroids. RESULTS Eight patients (47%) had increased latencies in at least one eye or showed increased interocular latency difference. Four patients (23%) presented a significant high signal intensity on T2-weighted brain MRI images. Of these 4 patients, 3 had prolonged VEP latency. Two patients with delayed VEP latency had antibodies against GM1, and SGLPG and anti-sulfatides, respectively. One patient with normal VEPs also had antibodies to GM1. VEP results were not significantly modified after treatment, either with steroids or IVIG. CONCLUSION This study confirmed the high frequency of abnormal VEPs in CIDP patients, and found that they are poorly correlated with CNS demyelinating lesions and antibodies against glycolipids. The VEP abnormalities of these patients may be explained by the susceptibility to immune-mediated damage of both the peripheral nervous system and the optic nerve.

Creutzfeldt-Jakob disease Neurophysiologic visual impairments

Objective: The predictive value of electrophysiologic visual testing in Creutzfeldt-Jakob disease (CJD) was investigated, and the retinal pathologic findings in three cases are reported. Background: The fatal prognosis of CJD, its transmissibility, and the lack of treatment make early diagnosis essential in averting human-to-human transmission. Electroretinogram and visual evoked potentials have been studied in few cases of CJD. Methods: A visual electrophysiologic examination was performed in 41 consecutive patients referred with suspected CJD. The disease had been diagnosed in 24 patients (CJD group; 15 were confirmed neuropathologically and 9 by clinicolaboratory methods in accordance with diagnostic criteria). The remaining 17 patients were diagnosed with other neurologic disorders, and served as a control group. Results: Flash electroretinogram revealed a significant decrease in the amplitude of the B1 wave (<60 µV) and the B/A ratio (<2) in the CJD group compared with those in the control group. Flash visual evoked potentials revealed no significant difference in latency, but amplitude was increased (>10 µV) in the CJD group, especially in patients with myoclonus. Conclusions: The visual electrophysiologic abnormalities provide an interesting noninvasive diagnostic tool in idiopathic CJD. The B1-wave decrease is closely correlated with the outer plexiform layer abnormalities observed on neuropathologic examination.

Pupillary disturbances in multiple sclerosis: correlation with MRI findings

UNLABELLED Autonomic nervous system disturbances such as pupillary abnormalities have rarely been evaluated in multiple sclerosis (MS). However, pupillary impairment is not uncommon in MS and its origin is still unclear. The aim of this study was to investigate pupillary disturbances in MS and to try to correlate pupillary defects with spinal cord and brainstem magnetic resonance imaging (MRI) findings. We prospectively studied 45 MS patients and 30 normal subjects. METHODS The pupillary contraction latency and the amplitude of contraction were recorded by pupillometry. We also determined afferent and efferent pathway defects by comparing the direct and consensual pupillary reflexes. We evaluated brainstem and spinal cord demyelinating lesions and spinal cord cross-sectional area on MRI. At least one pupillometric parameters were significantly impaired in 60% of patients and in none of the controls. We did not find any correlation between pupillary defect and demyelinating lesions on MRI. The most frequent abnormality was efferent pathway shift and this was correlated with spinal cord atrophy (P<0.02). These results confirm that the autonomic nervous system, and especially pupillary function, is frequently impaired in MS. The parasympathetic system is most commonly affected and this is most likely linked to axonal loss (demonstrated by spinal cord atrophy) rather than to demyelinating lesions.

The effect on vision of associated treatments in patients taking vigabatrin: carbamazepine versus valproate.

Summary:  Purpose: To evaluate the effect on visual function of a concomitant antiepileptic drug (AED) in patients treated with vigabatrin (VGB).

Resolution of acute acquired comitant esotropia after suboccipital decompression for Chiari I malformation

PURPOSE To report a case of acute comitant esotropia successfully treated with suboccipital decompression in a 9-year-old male patient with Chiari I malformation. DESIGN Interventional case report. METHODS A 9-year-old male with Chiari I malformation had acute onset of diplopia, headache, and comitant esotropia. RESULTS About 9 months after suboccipital decompression, diplopia resolved and there was near orthophoria on examination 15 months after surgery. CONCLUSION In view of our case and after a review of literature, we advocate primary suboccipital decompression to treat acute comitant esotropia in patients with Chiari I malformation. A follow-up period of at least 1 year rather than 6 months seems necessary to assess surgery effects.

Partially reversible quadruple sectoranopia caused by vascular steal due to an arteriovenous malformation.

BackgroundLateral, homonymous upper and lower field blind sectors sparing a horizontal zone define quadruple sectoranopia. This rare campimetric deficit involves ischemia or infarction of parts of the lateral geniculate body supplied by the distal anterior choroidal artery.MethodsA 41-year-old patient presented with a complaint of blurred vision. Visual acuity was 20/20 on both sides. Visual field showed a left quadruple sectoranopia. CT scan, MRI, MRA and conventional angiography showed a right cerebral arteriovenous malformation supplied partly by the right anterior choroidal artery. Partial retinal nerve fiber layer atrophy matched to the campimetric deficit proved that some degree of infarction involved the lateral geniculate body.ResultsThe arteriovenous malformation was treated with stereotactic radiosurgery. Two years after treatment, the nidus had completely disappeared. The campimetric deficit began improving from 19 months onwards after stereotactic radiosurgery. Twenty-eight months after treatment, the superior defect had completely reversed.ConclusionsQuadruple sectoranopia involves ischemia or infarction of parts of the lateral geniculate body supplied by the distal anterior choroidal artery. Following radio-induced angioma thrombosis, blood was no longer shunted away from the right lateral geniculate body, whose viable areas resumed their activity. Accordingly, a partial campimetric recovery occurred.

Multiple sclerosis with normalneuro‐ophthalmological work‐up:results of focal stimulations inducedby a scanning laser ophthalmoscope

Objective– Visual evoked potentials (VEPs) are a very useful tool in diagnosis of multiple sclerosis (MS). Nevertheless, in some cases of the disease, VEPs are normal. The aim of this study was to evaluate the diagnostic value of focal checkerboard reversal stimulation based on opto‐acoustic modulation generated by a scanning laser ophthalmoscope (SLO) in patients whose standard neuro‐ophthalmological work‐up was normal. Methods– We prospectively studied 185 MS patients. In this cohort we found 30 patients with definite MS and normal neuro‐ophthalmological work‐up and we studied the diagnostic yield of focal visual stimulation in these patients. We performed focal SLO‐elicited VEPs with two different spatial distributions: a central 8×8 degrees square field and a central 8×8 degrees exclusion square. The results were analysed in terms of age of the patient, course of the disease, and disability evaluated on the Expanded Disability Status Scale (EDSS). Results– Mean latencies of focal VEPs were increased in MS patients compared to controls. In MS, focal stimulation allowed dysfunction of the visual system to be detected in 50% of patients who have been classified as normal according to conventional VEPs. VEP abnormalities were found to be correlated with the EDSS score (P<0.001) and the course of the disease (P<0.05). Conclusion– We have demonstrated the value of focal VEPs in MS diagnosis using SLO‐based techniques. Further prospective work in patients with possible and probable MS should enable an evaluation of the sensitivity and specificity of this method in the early diagnosis of MS.