CANVAS: una nueva etiología de la ataxia del adulto. La asociación con tos orienta al diagnóstico. Comunicación de 2 pacientes / Late-Onset Cerebellar Ataxia with Neuropathy: Uncovering the Role of RFC1 Gene Mutations

Presentamos dos pacientes no relacionados con ataxia cerebelosa de inicio tardío asociada con neuropatía y tos seca de larga data. Un paciente tenía dos hermanos afectados con neuropatía sensorial y tos. Ambos probandos tuvieron investigaciones extensas que incluyó pruebas genéticas negativas para las ataxias más comunes, así como pruebas paraneoplásicas y otras causas inmunológicas. Ambos pacientes mostraron una expansión intrónica anormal en el pentanucleótido AAGGG del gen RFC1. Esta etiología se informa como causa frecuente de ataxia de inicio en adultos; la presencia de tos puede conducir al diagnóstico correcto.

We report two unrelated patients with late-onset cerebellar ataxia associated with neuropathy and a long-standing dry cough. One patient had two siblings affected with sensory neuropathy and cough. Both probands had extensive investigations including genetics testing negative for most common ataxias as well as testing for paraneoplasic and other immunologic causes. Both patients showed an abnormal intronic expansion in the pentanucleotide AAGGG of the gene RFC1. This etiology is being reported as frequent cause of adult-onset ataxia; the presence of cough may lead to the correct diagnosis.

Clinical characteristics and treatment analysis of the facial onset sensory and motor neuronopathy / 中风与神经疾病杂志

@#Objective　To retrospectively analyze the clinical characteristics and treatment of patients with facial onset sensory and motor neuronopathy (FOSMN).Methods　FOSMN syndrome were searched in PubMed,EMbase,CBM,CNKI,WanFang Data database,from the date of database establishment to 2019,and combined with a case admitted to our hospital.The clinical characteristics and treatment were analyzed from above data.Results　A total of 27 studies were included,42 males and 25 females,with an average onset age of (51.0±12.4) years.Clinical features:85.1% had numbness in the face or mouth as the initial symptom,53.7% had facial muscle weakness,56.7% had facial muscle atrophy,50.7% had abnormal corneal reflex,more than 80% had bulbar syndrome,and more than 50% had neck flexion or upper limbs weakness,47.8% had neck or upper limb muscle atrophy,and 43.3% had tongue muscle atrophy.Pathological examination of autopsy or muscle biopsy showed loss of involvement nucleus and spinal cord neurons,as well as muscle neurogenic atrophy.TDP-43-positive inclusions were found by autopsy.Neuroelectrophysiological examination:83.6% had prolonged or disappeared blink reflex,88.1% had acute or chronic progressive denervation,and 55.2% had lower SNAP amplitude in upper limbs.Treatment:Of the,1/30 cases had a clear improvement with IVIg therapy.Some patients continued to progress after IVIG,glucocorticoids,and plasma exchange therapy;16 patients were died with an average duration of 7.7 years.Conclusion　FOSMN syndrome begins with abnormal sensory in the trigeminal nerve distribution area.The lesions spread from top to bottom in the brainstem,gradually involving the motor nucleus in bulbar,and spinal cord anterior horn.The abnormal blink reflexes,neurogenic damage,and SNAPs amplitude reduction in neuroelectrophysiological examinations have diagnostic value.There is a high possibility of degenerative diseases and no effective treatment for the disease currently.

Neuronopatía sensitiva: Su reconocimiento y tratamiento temprano / Sensory neuronopathy. Its recognition and early treatment

Las neuronopatías o ganglionopatías sensitivas, o enfermedades del ganglio dorsal, representan un subgrupo de enfermedades del sistema nervioso periférico, frecuentemente asociadas a trastornos disinmunes o paraneoplásicos, y a agentes tóxicos. Los pacientes típicamente presentan ataxia temprana, pérdida de los reflejos osteotendinosos y síntomas sensitivos positivos, presentes tanto en partes proximales como distales del cuerpo. Estudiamos retrospectivamente 10 casos con un diagnóstico final de neuronopatía sensitiva. El síntoma de presentación fue el de una neuropatía sensitiva de curso subagudo en todos los casos, con parestesias en el 100% de los casos. Otras manifestaciones fueron: hipoestesia (10/10), ataxia de la marcha (8/10), síntomas autonómicos (3/10) y parestesias periorales (3/10). La electrofisiología mostró un patrón de compromiso sensitivo axonal, con respuestas motoras normales. El diagnóstico final fue neuronopatía sensitiva adquirida en todos, asociada a síndrome de Sjögren en dos, a lupus eritematoso en uno, a artritis reumatoidea en uno, a cáncer en dos (paraneoplásica) e idiopática en cuatro. En los casos paraneoplásicos, los tumores fueron un carcinoma de pulmón de células pequeñas (con anticuerpos anti-Hu positivos) y un carcinoma epidermoide de pulmón. Ocho pacientes fueron tratados con inmunoterapia, con altas dosis de metilprednisolona endovenosa y/o con inmunoglobulina endovenosa; con pobre respuesta en cuatro casos, mejoría neurológica en cinco, y sin cambios en uno. El presente trabajo muestra el patrón clinico y electrofisiológico de las neuronopatías sensitivas subagudas, y la relevancia de un tratamiento temprano.

Sensory neuronopathies or ganglionopathies, or dorsal root ganglion disorders, represent a subgroup of peripheral nervous system diseases, frequently associated with dysinmune or neoplastic disorders and with toxic agents. A degeneration of both central and peripheral sensory proyections is present. Patients typically show early ataxia, loss of deep tendon reflexes and positive sensory symptoms present both in proximal and distal sites of the body. We retrospectively studied 10 cases with a final diagnosis of sensory neuronopathy. Sensory neuropathy was the presenting symptom and the course was subacute in all cases. Paresthesias in upper limbs were a predominant manifestation (100%). Other manifestations included: hypoesthesia (10/10), gait ataxia (8/10), autonomic symptoms (3/10) and perioral paresthesias (3/10). Electrophysiology showed sensory axonal neuronal pattern, with normal motor responses. Final diagnosis was acquired sensory neuronopathy in all patients, associated with Sjögren’s syndrome in 2, with lupus erythematosus in 1, with rheumatoid arthritis in 1, with a cancer in 2 (paraneoplastic) and idiopathic in 4. In paraneoplastic cases, the tumor was small cell lung cancer in 1 (with positive anti-Hu antibodies), and epidermoid lung cancer in the other. Eight patients were treated with immunotherapy, high dose intravenous methylprednisolone and/or intravenous immunoglobulin; with poor response in 4 cases, neurologic improvement in 5, and without any change in 1 patient. The present work shows the typical clinical and electrophysiological pattern of subacute sensory neuronopathy, and the relevance of early treatment.

Miller Fisher syndrome/acute motor axonal neuronopathy overlap an atypical manifestation of malaria: a case report.

Various types of neurological manifestations are described in P. falciparum/vivax malaria of which Guillian Barre syndrome and its variant like Miller Fisher Syndrome (MFS) and Acute Motor Axonal Neuronopathy (AMAN). We are reporting such an unusual case who presented with five days history of fever and weakness of three days duration. On investigations it turned out to be acute MFS/AMAN overlap with peripheral blood showing mixed infection having heavy parasitaemia of P. falciparum and P. vivax combine. All other causes of acute polyneuropathy were ruled out by history and relevant examination. Patient improved with Artemisinin based Combination Therapy (ACT) and other supportive measures.

Ulnar sensory-motor amplitude ratio: a new tool to differentiate ganglionopathy from polyneuropathy / Razao de amplitude sensitivo-motora ulnar: novo parametro para diferenciar ganglionopatia de polineuropatia

The objective of this study was to evaluate if the ratio of ulnar sensory nerve action potential (SNAP) over compound muscle action potential (CMAP) amplitudes (USMAR) would help in the distinction between ganglionopathy (GNP) and polyneuropathy (PNP). Methods We reviewed the nerve conductions studies and electromyography (EMG) of 18 GNP patients, 33 diabetic PNP patients and 56 controls. GNP was defined by simultaneous nerve conduction studies (NCS) and magnetic resonance imaging (MRI) abnormalities. PNP was defined by usual clinical and NCS criteria. We used ANOVA with post-hoc Tukey test and ROC curve analysis to compare ulnar SNAP and CMAP, as well as USMAR in the groups. Results Ulnar CMAP amplitudes were similar between GNP x PNP x Controls (p=0.253), but ulnar SNAP amplitudes (1.6±3.2 x 11.9±9.1 × 45.7±24.7) and USMAR values (0.3±0.3 × 1.5±0.9 × 4.6±2.2) were significantly different. A USMAR threshold of 0.71 was able to differentiate GNP and PNP (94.4% sensitivity and 90.9% specificity). Conclusions USMAR is a practical and reliable tool for the differentiation between GNP and PNP. .

O objetivo deste estudo foi avaliar se a razão entre as amplitudes dos potenciais de ação sensitivo (SNAP) e motor (CMAP) do nervo ulnar (USMAR) auxiliaria na distinção entre ganglionopatia (GNP) e polineuropatia (PNP). Métodos Revisamos os estudos de neurocondução e eletromiografia de 18 pacientes com GNP, 33 com PNP diabética e 56 controles. GNP foi definida pela presença simultânea de anormalidades na neurocondução e na ressonância magnética cervical. PNP foi definida por critérios clínicos e neurofisiológicos usuais. Usamos o teste ANOVA com Tukey post-hoc e análise da curva ROC para comparar o SNAP e CMAP ulnares, assim como o USMAR entre os grupos. Resultados As amplitudes dos CMAPs ulnares foram similares entre GNP × PNP × Controles (p=0,253), mas as amplitudes dos SNAPs ulnares (1,6±3,2 × 11,9±9,1 × 45,7±24,7) e os valores de USMAR (0,3±0,3 × 1,5±0,9 × 4,6±2,2) foram significativamente diferentes. Um corte de 0,71 para a USMAR foi capaz de diferenciar GNP de PNP (sensibilidade de 94,4% e especificidade de 90,9%). Conclusões A USMAR é um parâmetro útil e confiável para o diagnóstico diferencial entre GNP e PNP. .

Cerebellar atrophy is frequently associated with non-paraneoplastic sensory neuronopathy / Atrofia cerebelar não é um achado frequente em pacientes com neuronopatia sensitiva não paraneoplasica

Sensory neuronopathies (SN) are peripheral nervous system disorders associated with degeneration of dorsal root ganglion neurons. Despite the evidence of a defective proprioceptive sensory input in SN,the prominent gait and truncal ataxia raises the question of a concomitant involvement of the cerebellum. OBJECTIVE: To evaluate cerebellar atrophy in SN. METHOD: We analyzed MRI-based volumetry of anterior lobe (paleocerebellum) and total cerebellum in patients with non-paraneoplastic chronic SN and compared to age- and gender-matched controls. RESULTS: Cerebellum and anterior lobe MRI volumetry were performed in 20 patients and nine controls. Mean anterior lobe and cerebellar volume were not statistically different. Three patients (15 percent), however, had an abnormal anterior lobe and cerebellar volume index (values outside 2.5 standard deviations). One of them also had a specific atrophy of the anterior lobe. All these patients had infectious or dysimmune associated SN. CONCLUSION: Cerebellar atrophy is infrequently associated with SN, but can be found in some patients with SN related to infectious or immune mediated conditions. It can be more prominent in the anterior lobe and may contribute to the ataxia seen in these patients.

Neuronopatias sensitivas (NS) são distúrbios do sistema nervoso periférico associados com a degeneração dos neurônios do gânglio da raiz dorsal. Apesar da evidência de um defeito das aferências proprioceptivas, a ataxia proeminente da marcha e do tronco levanta a questão de uma participação concomitante do cerebelo. OBJETIVO: Avaliar a atrofia cerebelar nas NS. MÉTODO: Foi analisada volumetria pela ressonância magnética do cerebelo total e do lobo anterior (paleocerebelo) em pacientes com NS crônica não-paraneoplásica e comparada a controles com idades e sexos correspondentes. RESULTADOS: A volumetria do cerebelo e lobo anterior foi realizada em 20 pacientes e nove controles. As médias do volume cerebelar e do lobo anterior não foram estatisticamente diferentes. Três pacientes, entretanto, tiveram um valor anormal do índice de volume cerebelar e do lobo anterior (valores fora de 2,5 desvios-padrão). Um deles tinha inclusive uma atrofia específica do lobo anterior. Todos esses pacientes tinham NS associada a doenças infecciosas ou disimunes. CONCLUSÃO: Atrofia cerebelar é raramente associada com SN, mas pode ser encontrada em alguns pacientes com NS relacionada com doenças infecciosas ou imunológicas. Esta atrofia pode ser mais proeminente no lobo anterior e pode contribuir para a ataxia observada nestes pacientes.

Tremor in X-linked recessive spinal and bulbar muscular atrophy (Kennedy's disease)

OBJECTIVE: To study tremor in patients with X-linked recessive spinobulbar muscular atrophy or Kennedy's disease. METHODS: Ten patients (from 7 families) with a genetic diagnosis of Kennedy's disease were screened for the presence of tremor using a standardized clinical protocol and followed up at a neurology outpatient clinic. All index patients were genotyped and showed an expanded allele in the androgen receptor gene. RESULTS: Mean patient age was 37.6 years and mean number of CAG repeats 47 (44-53). Tremor was present in 8 (80 percent) patients and was predominantly postural hand tremor. Alcohol responsiveness was detected in 7 (88 percent) patients with tremor, who all responded well to treatment with a β-blocker (propranolol). CONCLUSION: Tremor is a common feature in patients with Kennedy's disease and has characteristics similar to those of essential tremor.

Gabapentin Therapy for Acute Sensory Neuronopathy: A case report

Sensory neuronopathy (sensory ganglionitis), believed to be caused by an autoimmune attack against the dorsal root ganglia, has been recently linked with antiganglioside antibodies (anti-GD 1b). We present a case of idiopathic sensory neuronopathy with a positive anti-GD 1b IgG. The patient showed functional improvement with the use of gabapentin and immediately showed a resumption of symptoms when its use was stopped. Currently there is no proven therapy for sensory neuronopathy and the effect of immunosuppressive and intra venous immunoglobulin has been reported with mixed results. Also, there has been no research yet on the use and effect of gabapentin in sensory neuronopathy. This case shows that gabapentin alleviated neuropathic pain and tingling sensation in sensory neuronopathy. The authors believe that gabapentin modulated the voltage dependent calcium channels in the dorsal root ganglion and that this led to overall clinical and functional improvement. The curative or relieving effect of gabapentin in sensory neuronopathy still needs more research in the future.

A Case of Anti-Hu Associated Paraneoplastic Subacute Sensory Neuronopathy

Subacute sensory neuronopathy usually occurs as a paraneoplastic syndrome, occurring most frequently in small cell lung cancer. We report a 63-year-old male presenting typical symptoms of subacute sensory neuronopathy. Electrophysiologic studies showed diffuse sensory axonal degeneration and anti-Hu antibody was positive in his serum. We reevaluated pulmonary lesions formerly diagnosed as active pulmonary tuberculosis. Chest computed tomography showed two nodules and hilar lymphadenopathy, and by percutaneous needle biopsy, small cell lung cancer was diag-nosed.

A Case of Paraneoplastic Stiff-Person Syndrome Associated with Breast Cancer

Stiff-person syndrome (SPS) is a rare CNS disease characterized by progressive fluctuating rigidity and superimposed muscle spasms. We report a woman who developed stiff-person syndrome in association with breast cancer. A 55-year-old woman had progressive rigidity and intermittent muscle spasms, which predominantly occurred in her right shoulder muscles. Her symptoms were aggravated by unexpected stimuli or emotional stress, but relieved during sleep. Needle electromyography showed continuous motor unit activities in affected muscles, which were completely abolished by general anesthesia. An Anti-GAD antibody test was negative. She also disclosed a subacute sensory neuronopathy, confirmed by nerve conduction study and sural nerve biopsy. Chest CT scan revealed an enlargement of the right axillary lymph node, which was proved to be a metastatic ductal carcinoma of the right breast. The authors report the first case of paraneoplastic stiff-person syndrome with sensory neuropathy of axonal type, which is associated with breast cancer.

Acute Sensory Neuronopathy; Identified with Electrodiagnosis and Magnetic Resonance Imaging

We report a 13 year-old female child with a idiopathic acute sensory neuronopathy mimicking a sensory form of Guillain-Barr syndrome, identified with electrodiagnosis and spine MRI. Motor conduction results were normal, but sensory nerve action potentials were not evoked in all four extremities. On MRI of the whole spine, the diffuse gadolinium-enhancement of dorsal roots in the spinal canal was detected without evidence of intramedullary lesion. The clinical symptoms and electrodiagnostic abnormalities had persisted for more than 18 months follow-up.

A Case ot Acute sensory neuronopathy

We have had an opportunity to study a patient with acute sensory neuronopathy. The patient was a 32-yearold housewife; the rapidly spreaded tingling sensation along both arms and legs developed, rendering her severely ataxic. There was no history of antecedent illness, familial neurological disease, or exposure to toxins and special drugs. On examinations, there was no abnormality in her mental and cranial nerve function. There was no motor weakness. She showed the profound loss of kinesthetic sense which was acutely progressive and associated with severe sensory ataxia and pseudoathetosis. All tendon reflexes were absent. However, cutaneous senses were preserved. There was no significant abnormal laboratory finding except elevated CSF protein content. On electrophysiologic findings, the decrease in the amplitude of action potentials with only mild slowing of conduction velocities of sensory nerves were found even though motor nerve conduction studies were normal. Median and tibial somatosensory evoked potentials could be elicited, although the median N19 scalp response and tibial N45 waveforms were prolonged in latency. Plasmapheresis were provided; clinical features improved. However, the electrophy-siological abnormalites remained. Thus we wish to report an additional case of woman suffering from the acute sensory neuronopathy, complementing the cases described by Stemm, Schaumburg and Asbury.