Multifocal Motor Neuropathy with Persistent Conduction Block: The Seminal Case.

Although multifocal motor neuropathy (MMN) is now recognized as a distinct, albeit rare, neurological condition, the path to its recognition was long and winding. This article provides an insight into the medical history of MMN "patient zero" and the first scientific publication that led to the recognition of MMN by the medical community. Multifocal motor neuropathy is nowadays recognized as a disease that produces asymmetric muscle weakness and cramping, with spontaneous motor unit activity (fasciculations and myokymia) but without sensory disorder. From an electrophysiological point of view, the neuropathy is characterized by persistent conduction blocks that usually initially affect the proximal upper extremity. The path to recognizing this rare entity was long and winding. In this article, we describe the first known patient suffering from this disease and the scientific context of its emergence, leading to the first publication on the subject, written by Gérard Roth (1923-2006) and his colleagues at the Neurology Department of Geneva University Hospital (Switzerland) [Eur Neurol. 1986;25(6):416-23].

A historical review of the evolution of the Tardieu Scale.

There are many clinical assessment tools that can be used to quantify spasticity, one feature of the Upper Motor Neurone (UMN) syndrome. The focus of this short paper is on three; the Tardieu Scale, the Modified Tardieu Scale and the Australian Spasticity Assessment Scale, because a fundamental concept of these tests is their velocity dependent nature. Other bedside assessments such as the Modified Ashworth Scale examine hypertonicity, another feature of the UMN syndrome, but in this instance, the stretching movement is not velocity dependent. The Tardieu Scale, while not officially named until 1997, was conceived in the 1950s and since that time it has been revised by multiple authors and it is these additions that will be discussed in this article. The advantages and disadvantages of these assessment tools will be discussed with the ultimate aim of identifying one that has greater clinical utility.

Patterns of Weakness, Classification of Motor Neuron Disease, and Clinical Diagnosis of Sporadic Amyotrophic Lateral Sclerosis.

When approaching a patient with suspected motor neuron disease (MND), the pattern of weakness on examination helps distinguish MND from other diseases of peripheral nerves, the neuromuscular junction, or muscle. MND is a clinical diagnosis supported by findings on electrodiagnostic testing. MNDs exist on a spectrum, from a pure lower motor neuron to mixed upper and lower motor neuron to a pure upper motor neuron variant. Amyotrophic lateral sclerosis (ALS) is a progressive mixed upper and lower motor neuron disorder, most commonly sporadic, which is invariably fatal. This article describes a pattern approach to identifying MND and clinical features of sporadic ALS.

Neuropathy target esterase (NTE): overview and future.

Neuropathy target esterase (NTE) was discovered by M.K. Johnson in his quest for the entity responsible for the striking and mysterious paralysis brought about by certain organophosphorus (OP) esters. His pioneering work on OP neuropathy led to the view that the biochemical lesion consisted of NTE that had undergone OP inhibition and aging. Indeed, nonaging NTE inhibitors failed to produce disease but protected against neuropathy from subsequently administered aging inhibitors. Thus, inhibition of NTE activity was not the culprit; rather, formation of an abnormal protein was the agent of the disorder. More recently, however, Paul Glynn and colleagues showed that whereas conventional knockout of the NTE gene was embryonic lethal, conditional knockout of central nervous system NTE produced neurodegeneration, suggesting to these authors that the absence of NTE rather than its presence in some altered form caused disease. We now know that NTE is the 6th member of a 9-protein family called patatin-like phospholipase domain-containing proteins, PNPLA1-9. Mutations in the catalytic domain of NTE (PNPLA6) are associated with a slowly developing disease akin to OP neuropathy and hereditary spastic paraplegia called NTE-related motor neuron disorder (NTE-MND). Furthermore, the NTE protein from affected individuals has altered enzymological characteristics. Moreover, closely related PNPLA7 is regulated by insulin and glucose. These seemingly disparate findings are not necessarily mutually exclusive, but we need to reconcile recent genetic findings with the historical body of toxicological data indicating that inhibition and aging of NTE are both necessary in order to produce neuropathy from exposure to certain OP compounds. Solving this mystery will be satisfying in itself, but it is also an enterprise likely to pay dividends by enhancing our understanding of the physiological and pathogenic roles of the PNPLA family of proteins in neurological health and disease, including a potential role for NTE in diabetic neuropathy.

Ubiquitin-positive tau-negative intraneuronal inclusions in dementia with motor neuron disease: The 50th Anniversary of Japanese Society of Neuropathology.

We first reported ubiquitin-positive tau-negative intraneuronal inclusions in the hippocampal granular cell layer and entorhinal cortices in patients with amyotrophic lateral sclerosis (ALS). We then found that those inclusions occur frequently in patients with presenile dementia and motor neuron disease. The ultrastructure of the inclusions consists mainly of granules with a few filaments. In 2006, TDP-43 was identified as a major component of the inclusions specific for frontotemporal lobar degeneration and ALS. Here, we review the current knowledge regarding ubiquitin-positive tau-negative intraneuronal inclusions.

[Primary lateral sclerosis: the era of international diagnosis criteria]. / La sclérose latérale primitive : l'avènement de critères consensuels internationaux.

Since Charcot's first description, primary lateral sclerosis (PLS) remains a rare clinical syndrome, a neuropathological phenotype of motor system degeneration. In turn, PLS has been described as belonging to the large spectrum of motoneuron diseases or to the diverse degenerative diseases of the nervous system. Clinically, it is characterized by progressive pyramidal involvement in patients who present insidiously progressive gait disorders and, on examination, have relatively symmetrical lower limb weakness, increased muscle tone, pathologic hyper-reflexia, and exaggerated extensor plantar responses. Pinprick, light touch, and temperature sensations are preserved. Viewed in another way, PLS mimicks progressive hereditary spastic paraparesis (HSP) and the "central" phenotype of amyotrophic lateral sclerosis (ALS). PLS is considered "idiopathic" and, depending on the presence or absence of similarly affected family members, the syndrome of idiopathic HSP and ALS are labeled "hereditary" or "apparently sporadic". The juvenile form of PLS and early age at onset in cases of HSP complicate our understanding of the relationship between these two disorders. Guidelines for diagnosis and genetic counseling have been published for HSP and ALS. Recently, since the first international workshop, guidelines for diagnosis of PLS propose a classification system, e.g. for heterogeneous HSP into "pure PLS", complicated or "plus PLS", symptomatic PLS and upper motor neuron-dominant ALS. However, when reviewing known cases of PLS drawn from the literature, rigorous retrospective application of these new PLS criteria raises an unanswered question: does pure PLS exist?

A neuropathic syndrome of uncertain origin: review of 100 cases

The clinical features of 100 cases of a neuropathic syndrome observed in the University College Hospital of the West Indies over a period of 3½ years are described. The four main features are: (a) upper motor neuron damage (93) (b) damage to the first sensory neuron (c) retrobulbar neuropathy (d) eighth nerve deafness The onset is from the second to the sixth decade and may be sudden or gradual. The sex incidence is equal. Maximum incapacity occurs within a few months and the disease thereafter appears to be stationary. No pathological material has yet been available for study but the nature of the lesion and the possible causes are discussed. The diet of the patients varied from good to very poor but few showed overt signs of vitamin deficiency or mal-nutrition. A dietary factor is possibly responsible but there is no definite evidence of this.

Se describen las caracteristicas clinicas de 100 casos de un sindrome neuropatico observadas en el Hospital del University College durante un plazo de 3½ anos. Las cuatro caracteristicas principles son: (1) dano sufrido en el neuroma motor superior (93) (2) dano sufrido en le primer neuroma sensorio (3) neuropatia retrobulbar (4) sordera del octavo nervio Se registra el acceso de la enferndad entre la segunda y la sexta decada; puede ser repentino o paulatino. La incidencia en los dos sexos es igual. La incapacidad maxima ocurre dentro de unos pocos meses y después de esto la enfermedad parece establecerse en un estado estatica. Todavía no se han conseguido materiales patológicas para un estudio detenido; no obstante se describe la naturaleza de la lesión y las causas que pueden ocasionarla. La dieta de los pacientes variaba de buena a malísima pero pocos manifestaban senales evidentes de deficiencia de vitaminas ni de desnutrición. Puede que sea responsable un agente dietario pero de esto no tenemos evidencia definitiva.

The history of progressive muscular atrophy: syndrome or disease?

Since its first description more than a century ago, there has been much debate about the diagnostic entity progressive muscular atrophy (PMA). Initially, PMA included all forms of progressive amyotrophy. With the identification of several myogenic and neurogenic diseases and the recognition of amyotrophic lateral sclerosis (ALS), PMA was deemed to disappear as a nosologic entity at the end of the 19th century. In the last century, various other lower motor neuron syndromes were distinguished which may previously have been designated as cases of PMA. In contrast, several observations provided evidence that PMA can be linked both clinically and pathologically to ALS. Therefore, PMA should be considered as a syndromal subtype within a clinical spectrum of motor neuron diseases.