Miller Fisher syndrome (MFS) and Bickerstaff's Brainstem Encephalitis (BBE) share some clinical features and a common immunological profile characterized by anti-GQ1b antibodies. Some MFS patients ...overlap with Guillain-Barré syndrome (GBS) or BBE. We report a patient with MFS, BBE, and axonal GBS overlap in whom serial electrophysiological studies showed persistent motor conduction blocks (CBs).
A 61-year-old man acutely developed ophtalmoparesis, ataxia and areflexia suggesting MFS. Paresthesias, severe weakness, and drowsiness rapidly developed indicating an overlap with BBE and GBS. Preceding infection with Mycoplasma Pneumoniae and anti-GQ1b antibodies were detected. On day 4, nerve conduction study showed reduced or non-recordable compound muscle action potentials (CMAPs) and sensory nerve action potentials (SNAPs) without demyelinating features, indicating the electrodiagnosis of acute motor and sensory axonal neuropathy and suggesting a poor prognosis. Intravenous immunoglobulins (IVIg) were given but clinical status worsened to ophthalmoplegia, tetraplegia and coma needing mechanical ventilation. A second IVIg course was given and the patient was weaned off ventilation on day 41 and transferred to rehabilitation on day 57 with partial resolution of the ophthalmoplegia and limited recovery of muscle strength. Electrophysiology showed, after 10 weeks, greatly improved distal CMAP amplitudes suggesting the resolution of distal CBs while CBs in intermediate and proximal nerve segments emerged. CBs unusually persisted for four to 6 months without development of abnormal temporal dispersion. A third IVIg course was started on day 179 and the resolution of CBs mirrored the clinical improvement.
GQ1b gangliosides are expressed in the nodal region of oculomotor nerves, muscle spindle afferents, peripheral nerves and possibly in the brainstem reticular formation. Anti-GQ1b antibodies may explain the complex symptomatology and the overlap between MFS, BBE, and GBS. CBs that persisted and recovered without the development of temporal dispersion suggest that weakness was due to a sustained, antibody-mediated, attack at the nodal region inducing a non-demyelinating conduction failure as expression of an acute onset, long lasting, nodopathy. Serial electrophysiological studies allowed not only to understand the underlying pathophysiology and formulate a more correct prognosis but also to guide the treatment.
La stimulation nerveuse répétitive (SNR) est une technique fiable pour l’évaluation des maladies de la jonction neuromusculaire (JNM) et permet de confirmer un défaut de transmission neuromusculaire. ...Cependant, étant donné que la JNM est une synapse hautement spécialisée qui fait le lien entre le motoneurone et la fibre musculaire, une réponse réduite peut se produire dans un sous-groupe de patients atteints de myopathies héréditaires ou acquises ou de pathologies du motoneurone. La dépression transitoire du potentiel global d’action musculaire (PGAM) lors d’une SNR est une observation neurophysiologique bien documentée dans la myotonie congénitale récessive. Elle représente la contrepartie neurophysiologique de la faiblesse transitoire qui affecte souvent les patients au début d’un mouvement après le repos (Modoni, 2011). Plus rarement, le décrément a été démontré chez des patients atteints de myopathie centronucléaire ou de myopathie distale. Selon certains auteurs, la présence d’un décrément peut inciter à envisager une intervention pharmacologique pour améliorer la faiblesse musculaire (Elahi, 2019). Bien que les myopathies et les troubles de la jonction neuromusculaire soient généralement distincts, leur coexistence a été rapportée. Dans ces cas, l’identification d’un défaut de transmission neuromusculaire dans une myopathie héréditaire peut aider à établir un diagnostic moléculaire (Nicolau, 2019). Un décrément anormal a été également signalé dans nombreuses pathologies du motoneurone. Dans la sclérose latérale amyotrophique (SLA) par exemple, le décrément est de plus en plus reconnu comme un aspect physiopathologique important. Il a été rapporté que le décrément corrèle avec la réduction de la taille du PGAM (Wang, 2001). Cela est dû en partie au processus chronique de dénervation/réinnervation responsable de l’instabilité de la JNM (Hu, 2018) et en partie aux changements morphologiques de la JNM qui entraînent une diminution du facteur de sécurité (Bjornskov, 1975). En conclusion, la SNR à basse fréquence est utile pour identifier un défaut de la transmission neuromusculaire dans une grande variété de maladies, non seulement de la JNM, mais aussi du muscle ou de son nerf moteur. Elle peut être considérée comme un outil d’aide au diagnostic et au suivi de ces maladies.
To date, little is known about the usefulness of ultra-high frequency ultrasound (UHF-US, 50-70 MHz) in clinical practice for the diagnosis of dysimmune neuropathies. We present a prospective study ...aimed at comparing UHF-US alterations of nerves and fascicles in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), distal CIDP (d-CIDP) and anti-MAG neuropathy and their relationships with clinical and electrodiagnostic (EDX) features. 28 patients were included (twelve CIDP, 6 d-CIDP and 10 anti-MAG) and ten healthy controls. Each patient underwent neurological examination, EDX and UHF-US study of median and ulnar nerves bilaterally. UHF-US was reliable in differentiating immune neuropathies from controls when using mean and/or segmental nerve and/or fascicle cross-sectional area (CSA); furthermore, fascicle ratio (fascicle/nerve CSA) was a reliable factor for differentiating d-CIDP from other types of polyneuropathies. The fascicle CSA appears to be more increased in CIDP and its variant than in anti-MAG neuropathy. UHF-US offers information beyond simple nerve CSA and allows for a better characterization of the different forms of dysimmune neuropathies.
Hereditary sensory and autonomic neuropathy type 1 is an autosomal dominant neuropathy caused by the SPTLC1 or SPTLC2 variants. These variants modify the preferred substrate of serine palmitoyl ...transferase, responsible for the first step of de novo sphingolipids synthesis, leading to accumulation of cytotoxic deoxysphingolipids. Diagnosis of HSAN1 is based on clinical symptoms, mainly progressive loss of distal sensory keep, and genetic analysis. Aim: Identifying new SPTLC1 or SPTLC2 “gain-of-function” variants raises the question as to their pathogenicity. This work focused on characterizing six new SPTLC1 variants using in silico prediction tools, new meta-scores, 3D modeling, and functional testing to establish their pathogenicity. Methods: Variants from six patients with HSAN1 were studied. In silico, CADD and REVEL scores and the 3D modeling software MITZLI were used to characterize the pathogenic effect of the variants. Functional tests based on plasma sphingolipids quantification (total deoxysphinganine, ceramides, and dihydroceramides) were performed by tandem mass spectrometry. Results: In silico predictors did not provide very contrasting results when functional tests discriminated the different variants according to their impact on deoxysphinganine level or canonical sphingolipids synthesis. Two SPTLC1 variants were newly described as pathogenic: SPTLC1 NM_006415.4:c.998A>G and NM_006415.4:c.1015G>A. Discussion: The combination of the different tools provides arguments to establish the pathogenicity of these new variants. When available, functional testing remains the best option to establish the in vivo impact of a variant. Moreover, the comprehension of metabolic dysregulation offers opportunities to develop new therapeutic strategies for these genetic disorders.
The trigeminal autonomic cephalalgias (TACs), including cluster headache, paroxysmal hemicrania and SUNCT, are characterized by the cardinal combination of short-lasting unilateral pain and autonomic ...phenomena affecting the head. Hemicrania continua (HC) shares many clinical characteristics with TACs, including unilateral pain and ipsilateral autonomic features. Nevertheless, HC is separately classified in the revised International Classification of Headache Disorders (ICHD-II). Here, we describe the case of a 45-year-old man presenting an unusual concurrence of different forms of primary headaches associated with autonomic signs, including subsequently ipsilateral cluster headache, SUNCT and HC. This report supports the theory that common mechanisms could be involved in pathophysiology of different primary headache syndromes.
Introduction: Nerve ultrasound has been used increasingly in clinical practice as a complementary test for diagnostic assessment of neuropathies, but nerve biopsy remains invaluable in certain cases. ...The aim of this study was to compare ultra–high‐frequency ultrasound (UHF‐US) to histologic findings in progressive polyneuropathies. Methods: Ten patients with severe, progressive neuropathies underwent ultrasound evaluation of the sural nerve before nerve biopsy. Ultrasound data were compared with histologic results in a retrospective manner. Results: Sural nerves were easily identified on UHF‐US. Nerve hyperechogenicity correlated with inflammatory infiltrates on biopsy. Nerve fascicles could be identified and measured on ultrasound in the majority of patients. Discussion: Hyperechogenicity on UHF‐US may be a marker of nerve inflammation in neuropathies. Furthermore, the UHF‐US probe allows for evaluation of sensory nerves in spite of their small size, providing valuable information on their size and on their internal structure.
Author Affiliation: (1) Unite de Medecine Interne: Maladies Auto-immunes et Pathologie Vasculaire (UF 04), Centre de Reference des Maladies auto-immunes systemiques Rares d'Ile-de-France MATHEC ...(FAI2R), Assistance Publique-Hopitaux de Paris, 75010, Paris, France (2) Service de Medecine Interne et Maladies Infectieuses, CHU de Poitiers, 2, rue de la Miletrie, 86021, Poitiers cedex, France (3) CIC-1402, CHU de Poitiers, 2, rue de la Miletrie, 86021, Poitiers cedex, France (4) Service de Neurologie, National Reference Center for Familial Amyloid Polyneuropathy and Other Rare Neuropathies, Hopital Bicetre, Assistance Publique-Hopitaux de Paris, 94275, Le Kremlin-Bicetre, France (5) U1195, INSERM, Universite Paris-Saclay, 94276, Le Kremlin Bicetre, France (6) Service de Neurologie, CHU de Poitiers, 2, rue de la Miletrie, 86021, Poitiers cedex, France (7) Centre Hospitalier Universitaire de Nice, Systeme Nerveux Peripherique et Muscle, Universite Cote D'Azur, Hopital Pasteur, 2, 30 voie Romaine, CS 51069, 06001, Nice Cedex 1, France (8) Service de Neurologie, Hopital Rangueil, CHU Toulouse, Avenue Jean Poulhes, 31300, Toulouse, France (9) Service de Medecine Interne, Hopital Purpan, CHU Toulouse, Place du Docteur Joseph Baylac, 31300, Toulouse, France (10) Faculte de Medecine de Toulouse, 37 Allee Jules Guesde, 31000, Toulouse, France (11) Institut Gustave-Roussy, Service d'hematologie, 114, rue Edouard-Vaillant, 94800, Villejuif, France (12) IRSL, Recherche Clinique Appliquee a l'Hematologie, EA3518, Universite de Paris, Paris, France (13) Department of Medicine, H3A 1A1, McGill University, Montreal, QC, Canada (a) fanny.urbain@aphp.fr Article History: Registration Date: 02/06/2021 Received Date: 11/26/2020 Accepted Date: 02/05/2021 Online Date: 03/02/2021 Byline:
Background
Mutations in the GNE gene have been so far described as predominantly associated with distal lower‐limb myopathies. Recent reports describe mutations in this gene in patients with ...peripheral neuropathy and motor neuron disease.
Methods
We describe three patients displaying motor neuropathy in association with GNE mutations. Clinical, electrophysiological, imaging, pathological, and genetic data are presented in a retrospective manner.
Results
The three patients had different phenotypes, ranging from mildly progressive lower limb weakness to a rapidly progressive 4‐limb weakness. Genetic testing revealed GNE gene mutations in all patients; of those mutations, p.(His186Arg) has not been previously reported. All patients showed evidence of axonal motor nerve involvement on electrodiagnostic examination and/or muscle biopsy.
Conclusions
Nerve involvement associated with GNE gene mutations may be an underdiagnosed pathology and may influence clinical presentation and disease progression.
CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, immunoglobulin M IgM paraprotein, cold agglutinins, and disialosyl antibodies) is a rare syndrome characterized by chronic neuropathy with sensory ...ataxia, ocular, and/or bulbar motor weakness in the presence of a monoclonal IgM reacting against gangliosides containing disialosyl epitopes. Data regarding associated hematologic malignancies and effective therapies in CANOMAD are scarce. We conducted a French multicenter retrospective study that included 45 patients with serum IgM antibodies reacting against disialosyl epitopes in the context of evocating neurologic symptoms. The main clinical features were sensitive symptoms (ataxia, paresthesia, hypoesthesia; n = 45, 100%), motor weakness (n = 18, 40%), ophthalmoplegia (n = 20, 45%), and bulbar symptoms (n = 6, 13%). Forty-five percent of the cohort had moderate to severe disability (modified Rankin score, 3-5). Cold agglutinins were identified in 15 (34%) patients. Electrophysiologic studies showed a demyelinating or axonal pattern in, respectively, 60% and 27% of cases. All patients had serum monoclonal IgM gammopathy (median, 2.6 g/L; range, 0.1-40 g/L). Overt hematologic malignancies were diagnosed in 16 patients (36%), with the most frequent being Waldenström macroglobulinemia (n = 9, 20%). Forty-one patients (91%) required treatment of CANOMAD. Intravenous immunoglobulins (IVIg) and rituximab-based regimens were the most effective therapies with, respectively, 53% and 52% of partial or better clinical responses. Corticosteroids and immunosuppressive drugs were largely ineffective. Although more studies are warranted to better define the optimal therapeutic sequence, IVIg should be proposed as the standard of care for first-line treatment and rituximab-based regimens for second-line treatment. These compiled data argue for CANOMAD to be included in neurologic monoclonal gammopathy of clinical significance.
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