Atypical Motor Neuron Disease variants: Still a diagnostic challenge in Neurology.

Motor neuron disease (MND) represents a wide and heterogeneous expanding group of disorders involving the upper or lower motor neurons, mainly represented by amyotrophic lateral sclerosis (ALS), primary lateral sclerosis, progressive muscular atrophy and progressive bulbar palsy. Primary motor neuronopathies are characterized by progressive degenerative loss of anterior horn cell motoneurons (lower motor neurons) or loss of giant pyramidal Betz cells (upper motor neurons). Despite its well-known natural history, pathophysiological and clinical characteristics for the most common MND, atypical clinical presentation and neurodegenerative mechanisms are commonly observed in rare clinical entities, so-called atypical variants of MND-ALS, including flail-leg syndrome, flail-arm syndrome, facial-onset sensory and motor neuronopathy (FOSMN), finger extension weakness and downbeat nystagmus (FEWDON-MND) and long-lasting and juvenile MND-ALS. Herein, we provide a review article presenting clinical, genetic, pathophysiological and neuroimaging findings of atypical variants of MND-ALS in clinical practice.

New findings in facial-onset sensory and motor neuronopathy (FOSMN) syndrome.

Facial-onset sensory and motor neuronopathy (FOSMN) syndrome represents a rare, slowly progressive, lower motor neuron disease with sensory compromise, involving mainly the face, bulbar region and upper limbs. However, non-motor symptoms and neurogenetic studies have rarely been evaluated in large case series. In the present study, 10 unrelated Brazilian patients with FOSMN syndrome underwent extensive clinical, laboratory, neurophysiological and neurogenetic assessment. Median age at symptom onset was 52.1 years, and men and women were equally affected. Patients presented with hemifacial or bilateral facial paresthesia and weakness, which evolved with dysphagia, dysphonia, and facial and tongue atrophy and, finally, a dropped-head, upper limb weakness and syringomyelia-like sensory disturbances in the upper limbs. All 10 patients showed chronic diffuse neurogenic compromise of bulbar, cervical and thoracic myotomes, and abnormal blink reflex tests. A positive family history of neurodegeneration was identified in six cases, and revealed pathogenic gene variants in three families (involving VCP, TARDBP and CHCHD10). Thus, our case series has revealed new findings regarding FOSMN syndrome: (i) its clinical course is not always benign, with poorer prognoses associated with dropped-head syndrome and early bulbar compromise; (ii) FOSMN syndrome may be part of a complex familial neurodegenerative spectrum; and (iii) a definite genetic basis may be observed in some cases.

O'Sullivan-McLeod syndrome: Unmasking a rare atypical motor neuron disease.

Atypical motor neuron disease represents a rare heterogeneous group of neurodegenerative disorders with clinical, genetic and neuroimaging features distinct from those of the classic spinal or bulbar-onset amyotrophic lateral sclerosis (ALS). O'Sullivan-McLeod syndrome represents an extremely rare lower motor neuronopathy with early adult-onset distal amyotrophy and weakness in the upper limbs with asymmetrical involvement. To add to the few case series and epidemiological and genetic studies describing this variant syndrome, our team here presents a series of seven unrelated Brazilian patients with O'Sullivan-McLeod syndrome in a detailed review of their clinical, neuroimaging, laboratory and neurophysiological findings. A male-to-female ratio of 2.5 to 1 and a mean age at onset of 34.3years was observed, with a mean time delay of 6.6years between symptom-onset and a definitive diagnosis. A positive family history was observed in one case, yet whole-exome sequencing results were negative. Neuroimaging studies were unremarkable. All cases presented with chronic denervation restricted to cervical myotomes and normal sensory nerve conduction studies. This case series, one of the largest groups of patients with O'Sullivan-McLeod syndrome reported in the literature, confirms the sporadic nature of the condition and the difficulties faced in arriving at a definite diagnosis, and also expands the age limit in late adult-onset cases.

Eating epilepsy.

Eating epilepsy is a rare type of reflex epilepsy. A 24 years-old male with eating reflex complex partial seizures was submitted to clinical, neurological, neuroradiological and EEG studies. Neurologic and CT examinations were normal. EEG recordings including video-EEG monitoring during meals disclosed focal abnormalities related to both temporal lobes prevailing at the left side and secondary bilateral synchrony mainly in more anterior regions. Ictal findings were similar to the interictal secondary bilateral synchrony except for its longer duration. PB, VPA and DPH monotherapies were ineffective. High dose CBZ monotherapy yielded good but incomplete seizure control. Since a big number of precipitants could be involved, no specific physiopathological basis could be established.

Eating epilepsy

A epilepsia reflexa ao comer é uma rara de epilepsia reflexa. Um paciente de 24 anos com crises parciais complexas reflexas ao comer foi submetido a avaliaçöes clínica, neurológica neurorradiológica e eletrencefalográfica. O exame neurológico e a tomografia de crânio foram normais. Registros de EEG, incluindo menitorizaçäo vídeo-EEG durante a refeiçäo, mostraram presença de anormalidades focais relacionadas a ambos os lobos temporais, predominando à esquerda, e sincronia bilateral secundária, predominando em regiöes anteriores. Os achados ictais säo semelhantes à sincronia bilateral secundária interictal exceto por sua maior duraçäo. Monoterapias com PB, DPH e VPA näo surtiram efeito. Monoterapia com altas doses de CBZ trouxe bons resultados porém com controle incompleto das crises. Como grande número de fatores precipitantes estava potencialmente envolvido, näo foi possível determinar com precisäo a base fisiopatológica das crises reflexas neste caso

Non-epileptic myoclonus and mitochondrial encephalomyopathy.

Two brothers presented to us with a progressive myoclonic syndrome with slight cerebellar symptoms. Neurological examination disclosed moderate cerebellar signs and pale optic discs; asymmetric, asynchronous and arrhythmic myoclonus, an arrthesthesic deficit and no muscular weakness. EEG background activity was moderately slow with no irritative discharges. CT was normal in both cases. Intermittent photic stimulation increased the frequency of the myoclonic jerks, which became bilateral and synchronous, progressing to a generalized tonic-clonic seizure. EPs and MRI in one case were normal. Anticonvulsant drugs were ineffective. The diagnosis of mitochondrial encephalomyopathy was based on the finding, in muscle specimens, of thickened basement membranes with myofibrillary degeneration and increased number of mitochondria peripherally distributed and with a dense granular matrix and some vacuoles. The clinical and EEG data suggest a subcortical origin for this type of myoclonic syndrome.

Non-epileptic myclonus and mitochondrial encephalomyopathy

Foram examinados dois irmäos portadores de uma síndrome miclónica progressiva comn discretos sintomas cerebelares. O exame neurológico mostrava sinais cerebelares moderados e papilas pálidas; mioclonais assíncronas, arrítmicas e assimétricas, um déficit artrestésico e ausência de fraqueza muscular. A atividade de base do EEG era moderadamente lenta e sem atividade irritativa. A TC era normal em ambos os casos. A estimulaçäo fótica intemitente aumentava a freqüência dos abalos mioclônicos que se tornavam bilaterais e sincronos, progredindo para uma crise tônico-clônica generalizada. Potenciais evocados e RMN em um caso foram normais . Drogas anticonvulsivantes foram ineficazes no controle das mioclonias. O diagníostico de encefalomiopatia mitocondrial foi realizado através do achado em espécimes musculares de membranas basais espessadas, com degeneraçäo miofibrilar e um número elevado de mitocondrias distribuídos perifericamente e com uma matriz densa, granular e com alguns vacúolos. Os achados clínicos e eletrográficos sugerem uma origem subcortical para esta síndrome mioclônica