Epidemiology of ataxia and hereditary spastic paraplegia in Spain: A cross-sectional study.

INTRODUCTION: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. PATIENTS AND METHODS: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. RESULTS: We gathered data from a total of 1933 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 938 patients were men (48.5%) and 995 were women (51.5%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. CONCLUSIONS: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.

Practical recommendations for the clinical evaluation of patients with hereditary ataxia and hereditary spastic paraplegia.

Hereditary ataxia (HA) and hereditary spastic paraplegia (HSP) are rare diseases; as such, they are rarely managed in general neurology consultations. We present a set of brief, practical recommendations for the diagnosis and management of these patients, as well as a standardised procedure for comprehensive evaluation of disability. We provide definitions for HA and "HA plus," and "pure" and "complicated" HSP; describe the clinical assessment of these patients, indicating the main complementary tests and clinical scales for physical and psychological assessment of the patients; and summarise the available treatments. These recommendations are intended to facilitate daily neurological practice and to unify clinical criteria and disability assessment protocols for patients with HA and HSP.

Epidemiology of ataxia and hereditary spastic paraplegia in Spain: a cross-sectional study. / Mapa epidemiológico transversal de las ataxias y paraparesias espásticas hereditarias en España.

INTRODUCTION: Ataxia and hereditary spastic paraplegia are rare neurodegenerative syndromes. We aimed to determine the prevalence of these disorders in Spain in 2019. PATIENTS AND METHODS: We conducted a cross-sectional, multicentre, retrospective, descriptive study of patients with ataxia and hereditary spastic paraplegia in Spain between March 2018 and December 2019. RESULTS: We gathered data from a total of 1.809 patients from 11 autonomous communities, provided by 47 neurologists or geneticists. Mean (SD) age in our sample was 53.64 (20.51) years; 920 patients were men (50.8%) and 889 were women (49.2%). The genetic defect was unidentified in 920 patients (47.6%). A total of 1371 patients (70.9%) had ataxia and 562 (29.1%) had hereditary spastic paraplegia. Prevalence rates for ataxia and hereditary spastic paraplegia were estimated at 5.48 and 2.24 cases per 100 000 population, respectively. The most frequent type of dominant ataxia in our sample was SCA3, and the most frequent recessive ataxia was Friedreich ataxia. The most frequent type of dominant hereditary spastic paraplegia in our sample was SPG4, and the most frequent recessive type was SPG7. CONCLUSIONS: In our sample, the estimated prevalence of ataxia and hereditary spastic paraplegia was 7.73 cases per 100 000 population. This rate is similar to those reported for other countries. Genetic diagnosis was not available in 47.6% of cases. Despite these limitations, our study provides useful data for estimating the necessary healthcare resources for these patients, raising awareness of these diseases, determining the most frequent causal mutations for local screening programmes, and promoting the development of clinical trials.

Antidisialosyl antibodies in chronic idiopathic ataxic neuropathy.

Antidisialosyl antibodies were found in two out of 13 patients with chronic idiopathic ataxic neuropathy (CIAN) and not in 32 patients with different sensory neuropathies of known cause. This finding confirms the association of antidisialosyl antibodies and CIAN regardless of the absence of the M band. These antibodies may have pathogenic relevance; however, larger series are needed to establish their clinical significance.

Antiganglioside antibodies in acute self-limiting ataxic neuropathy: incidence and significance.

Antidisialosyl antibodies have been previously associated to chronic and acute ataxic neuropathies. We studied the presence of these antibodies in nine patients with acute self-limiting ataxic neuropathy (ASLAN) using ELISA and TLC immunodetection. One patient showed serum IgG immunoreactivity against gangliosides GD3 and GQ1b. The patient's IgG was able to bind to the nodes of Ranvier on frozen human dorsal root. Our studies confirmed that antidisialosyl reactivity is associated to ataxic neuropathy and its specific binding to the dorsal root could explain the predominant sensory involvement. Nevertheless, the low incidence of this reactivity indicates that a different pathogenic mechanism should be involved in most ASLAN patients.

[Antiganglioside antibodies: when, which and for what]. / Anticuerpos antigangliósido: cuándo, cuál y para qué

BACKGROUND: We report our experience in the study of antiganglioside antibodies and define their clinical value establishing associations between clinical syndromes and immunological findings. METHODS: We analysed 275 sera: Guillain-Barré syndrome (GBS) (78), Miller-Fisher syndrome (MFS) (37), chronic inflammatory demyelinating polyneuroapthy (CIDP) (17), multifocal motor neuropathy (NMM) (42), chronic axonal mixed polyneuropathy (PNP) (54), amyotrophic lateral sclerosis (ALS) (28) and lower motor neuron disease (LMND) (17). We have studied the presence of IgG and IgM antibodies to 9 gangliosides using ELISA and TLC. RESULTS: We have detected anti-GQ1b antibodies in 36/37 (97,3%) of patients with MFS, being undetectable after 4 weeks in 83%. A 34 % (26/78) of patients with GBS were positive for several antiganglioside specificities being GalGalNAc the most frequent (54%). Two out of three sera positive for GD1a corresponded to axonal Guillain-Barré. IgM class anti-GM1 antibodies were positive in 10/12 patients with MMN, while only a 3-9% of patients with ALS, CIDP, PNP and LMND presented antiganglioside antibodies. CONCLUSIONS: Analysis of anti-GQ1b antibodies confirms the diagnosis of MFS, excluding other acute brainstem pathologies and, in this study, detection of anti-GD1a antibodies indicates axonal damage in GBS and suggest a worse prognosis. IgM anti-GM1 antibodies are only found in MMN. These findings confirm a disease specific correlation between specific neuropathies and antiganglioside antibodies clinically useful.

Anticuerpos antigangliósido: cuándo, cuál y para qué / Antiganglioside antibodies: when, which and for what

FUNDAMENTO: Comunicamos nuestra experiencia en el estudio de anticuerpos antigangliósido y definimos su valor en la práctica clínica estableciendo asociaciones entre síndromes clínicos y hallazgos inmunológicos. MÉTODOS: Se analizaron 273 sueros: síndrome de Guillain-Barré (SGB), 78; síndrome de Miller-Fisher (SMF), 37; polineuropatía inflamatoria desmielinizante crónica (CIDP), 17; neuropatía motora multifocal (NMM), 42; polineuropatía mixta axonal crónica (PNP), 54; esclerosis lateral amiotrófica (ELA), 28, y enfermedad de segunda motoneurona (LMND), 17. Se ha estudiado la presencia de anticuerpos IgG o IgM frente a 9 gangliósidos mediante ELISA y CCF. RESULTADOS: Se han detectado anticuerpos anti-GQ1b en 36/37 de los pacientes (97,3 por ciento) con SMF, que en un 83 por ciento se negativizaron a las 4 semanas. El 34 por ciento (26/78) de los pacientes con SGB fueron positivos para diversas especificidades de antigangliósido, siendo GalGalNAc la más frecuente (54 por ciento). De los tres sueros positivos para GD1a, dos de ellos tenían un SGB axonal.Los anticuerpos antigangliósido de la clase IgM fueron positivos en 10 pacientes con NMM. Únicamente entre un 3 y un 9 por ciento de los sueros fueron positivos para alguna especificidad antigangliósido en los pacientes con ELA, CIDP, PNP y LMND. CONCLUSIONES: La determinación de anticuerpos anti-GQ1b confirma el diagnóstico de SMF excluyendo otras patologías agudas del tronco cerebral, y en este estudio el hallazgo de anticuerpos anti-GD1a se asocia a enfermedad axonal en el SGB e indica un peor pronóstico. La asociación IgM GM1 sólo se encuentra en enfermos con neuropatía motora multifocal. El conjunto de hallazgos confirma que existe una correlación enfermedad específica entre algunas neuropatías y determinados anticuerpos antigangliósido con utilidad clínica (AU)

[Anti-GQ1b antibodies: usefulness of its detection for the diagnosis of Miller-Fisher syndrome]. / Anticuerpos anti-GQ1b: utilidad de su determinación en el diagnóstico del síndrome de Miller-Fisher.

BACKGROUND: To study the presence of anti-GQ1b antibodies as a tool for the diagnosis of Miller-Fisher syndrome (MFS). PATIENTS AND METHOD: We studied 54 patients with probable diagnosis of MFS and 10 patients diagnosed as Guillain-Barré syndrome plus ophthalmoplegia (1 case), Bickerstaff's encephalitis (1 case), relapsing ophthalmoplegia (7 cases) and relapsing diplopia (1 case). Results were compared with 130 patients with other disimmune neuropathies. Antibodies were detected by ELISA and checked by thin layer chromatography. Campylobacter jejuni serology was studied using a complement fixation test. RESULTS: Diagnosis of MFS was confirmed in 38 patients. A 97.3% were positive for GQ1b, being all negative for Campylobacter jejuni serology. A second test after 4-5 weeks of nadir was negative in 84.2% (16/19), concomitant with clinical recovery. CONCLUSIONS: Anti-GQ1b antibodies are useful markers for the differential diagnosis of MFS, specially with some acute brainstem disorders. Testing must be performed during the first four weeks of clinical course. This correlation between the triad ataxia, arreflexia and ophthalmoplegia and anti-GQ1b antibodies confirms that they are highly specific of MFS.

Distal anterior compartment myopathy: a dysferlin mutation causing a new muscular dystrophy phenotype.

We report a family with a new phenotype of autosomal recessive muscle dystrophy caused by a dysferlin mutation. The onset of the illness is distal, in the muscles of the anterior compartment group. The disease is rapidly progressive, leading to severe proximal weakness. Muscle biopsy showed moderate dystrophic changes with no vacuoles. Dysferlin immunostaining was negative. Gene analysis revealed a frameshift mutation in the exon 50 (delG5966) of the DYSF gene. This phenotype further demonstrates the clinical heterogeneity of the dysferlinopathies.

[Therapeutic advances in neuromuscular diseases]. / Avances terapéuticos en enfermedades neuromusculares.

The etiology of neuromuscular diseases varies widely as does their treatment. This study reports the treatment of patients with neuromuscular disease of autoimmune origin in addition to the therapy of muscular dystrophies. The mechanisms of action of the immunosuppressive drugs (glucocorticoids, azathiaprin, cyclosporin, methotrexate, chlorambucil, cyclophosphamide) and immunomodulators (plasmapheresis, Ig ev) currently used are analyzed, as are their indications, management and the methods which allow the control of therapeutic efficacy. The immunotherapies presently in experimental phases are also reviewed (oral tolerance, inhibition of cytokines, chemokines, etc.). Both molecular therapy (myoblast transplantation, genetic therapy, gentamycin) and anabolizing drugs administered after the favorable results of clinical trials (glucocorticoids, oxandrolone) and undergoing controlled clinical studies (albuterol, creation, etc.) on the treatment of muscular dystrophies are evaluated. Lastly, symptomatic treatments which improve the quality of life of patients with muscular dystrophy are analyzed.