Quality of life in hereditary neuropathy with liability to pressure palsies is as impaired as in Charcot-Marie-Tooth disease type 1A.

To date, only one study assessed quality of life (QoL) in patients with hereditary neuropathy with liability to pressure palsies (HNPP). We aimed to fill in this gap by investigating QoL in a cohort of patients with HNPP compared to Charcot-Marie-Tooth type 1A (CMT1A) patients, as well as to analyze sociodemographic and clinical features associated with QoL in HNPP. Eighteen genetically confirmed HNPP patients were age-and gender-matched with 18 CMT1A patients. SF-36 questionnaire was used to assess QoL. Medical Research Council (MRC) Sum Score, CMT Neuropathy Score (CMTNS), Overall Neuropathy Limitation Scale Score (ONLS), Falls Efficacy Score (FES), Visual Analog Pain Scale, Beck Depression Inventory (BDI) and Fatigue Severity Scale (FSS) were also used in our study. Although HNPP patients were less clinically impaired, no difference was observed in these two cohorts regarding SF-36 scores. Worse QoL in HNPP patients was associated with lower education (p < 0.01), physical work (p < 0.05), higher number of clinically affected nerves during the disease course (p < 0.01), worse MRC-SS score (p < 0.01), worse ONLS score (p < 0.01), and with more severe pain (p < 0.01), depression (p < 0.01), and fatigue (p < 0.01). Worse pain at the moment of testing appeared as a significant independent predictor of worse QoL in HNPP patients (ß = - 0.93, p < 0.001). QoL was similarly impaired in patients with HNPP and patients with CMT1A. We identified different factors associated with QoL in HNPP, and many of these factors are amenable to treatment which is of special interest in these still incurable disease.

Facial onset sensory and motor neuronopathy: a motor neuron disease with an oligogenic origin?

Objective: To describe a patient with facial onset sensory and motor neuronopathy (FOSMN) carrying heterozygous mutations in both TARDBP and SQSTM1 genes. Methods: The patient underwent neurological, neuropsychological, and neurophysiological examinations. Brain magnetic resonance imaging (MRI) and extensive genetic analysis were also performed. Results: The neurological examination showed dysphonia, left trigeminal hypesthesia, and left masseter and temporalis muscle atrophy. Mild cognitive impairment, affecting predominantly executive functions and social cognition, was appreciable in the neuropsychological examination. The electrophysiological studies revealed: left abnormal blink reflex; neurogenic changes in bulbar and cervical muscles; normal motor evoked potential amplitude, central motor conduction time and cortical silent period. Brain MRI showed right-predominant frontotemporal atrophy. Genetic analysis showed a heterozygous mutation in TARDBP (p.A390S) and in SQSTM1 (p.P392L), both previously described as causing amyotrophic lateral sclerosis. The SQSTM1, but not the TARDBP, mutation was found in both healthy siblings. Conclusions: Our data provide new clinical, neuroimaging, and genetic evidence that FOSMN is a neurodegenerative disease of the motor neuron disease and frontotemporal dementia spectrum, with a possible oligogenic origin. Multicentric efforts focusing on cognitive and genetic studies are necessary to confirm this hypothesis and to determine if ALS genes should be systematically screened in these patients.

Funcionamiento Cognitivo Global y Conducta Adaptativa en dos Niñas con Neuropatía Sensitiva Autonómica Hereditaria Tipo IV / Global cognitive and adaptive functioning in two girls with hereditary sensory and autonomic neuropathy type IV

La neuropatía sensitiva autonómica hereditaria tipo IV (HSAN-IV) es una condición neurológica de origen genético extremadamente rara que puede cursar con discapacidad intelectual, sin embargo, hay escasas publicaciones sobre las características del funcionamiento cognitivo global y la conducta adaptativa de los afectados. En este estudio se describe la capacidad cognitiva global y el funcionamiento adaptativo de dos niñas de 12 y 14 años diagnosticadas con HSANIV, incluyendo una caracterización de los procesos de comprensión verbal, razonamiento perceptual, memoria de trabajo y velocidad de procesamiento. Las menores fueron evaluadas mediante la Escala de Inteligencia para niños de Wechsler cuarta edición (WISC-IV) encontrándose en ambos casos un bajo índice de comprensión verbal, una medida del desarrollo cognitivo alcanzado a través de la historia de aprendizaje de las niñas; así como un bajo índice de razonamiento perceptivo, indicador de su capacidad para adaptarse y afrontar situaciones nuevas de forma flexible. Esto se acompaña de dificultad en la manipulación de información en la memoria para la resolución de problemas y enlentecimiento en la velocidad de procesamiento de la información. Adicionalmente, se evaluó su funcionamiento adaptativo mediante el sistema de evaluación de la conducta adaptativa ABAS-II, el cual se caracterizó por fortalezas en habilidades comunicativas, uso de recursos comunitarios y vida en el hogar; con limitaciones en habilidades académicas y de autocuidado. En conclusión, la HSAN-IV es una condición que cursa con discapacidad intelectual con necesidades de apoyo variables en intensidad. En los casos estudiados se encontró discapacidad intelectual con necesidad de apoyo limitado, es decir, los apoyos se requieren de forma regular durante un periodo de tiempo corto pero definido.

Hereditary sensory autonomic neuropathy type IV (HSAN-IV) is a neurological condition of extremely rare genetic origin that may be associated with intellectual disability; however, there are few publications about the characteristics of global cognitive functioning and adaptive behaviour of these patients. In this study we describe the global cognitive function and the adaptive behavior of two girls aged 12 and 14 diagnosed with HSAN-IV, including a characterization of the processes of verbal comprehension, perceptual reasoning, working memory and processing speed. The children were assessed using the Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV), finding in both cases a low level of verbal comprehension, a measure of cognitive development achieved through the girls' learning history; as well as a low rate of perceptual reasoning, indicator of their ability to adapt and face new situations in a flexible way. This is accompanied by difficulty in manipulating information in the memory to solve problems and slow down the speed of information processing. Additionally, its adaptive functioning was evaluated through the Adaptive Behavior Assessment System ABAS-II, which was characterized by strengths in communication skills, use of community resources and life at home; with limitations in academic and self-care skills. In conclusion, HSAN-IV is a condition related with intellectual disability with varying support needs in intensity. In the cases studied, intellectual disability was found with limited need for support, that is, supports are required on a regular basis for a short but defined period.

Disturbances in affective touch in hereditary sensory & autonomic neuropathy type III.

Hereditary sensory and autonomic neuropathy type III (HSAN III, Riley-Day syndrome, Familial Dysautomia) is characterised by elevated thermal thresholds and an indifference to pain. Using microelectrode recordings we recently showed that these patients possess no functional stretch-sensitive mechanoreceptors in their muscles (muscle spindles), a feature that may explain their lack of stretch reflexes and ataxic gait, yet patients have apparently normal low-threshold cutaneous mechanoreceptors. The density of C-fibres in the skin is markedly reduced in patients with HSAN III, but it is not known whether the C-tactile afferents, a distinct type of low-threshold C fibre present in hairy skin that is sensitive to gentle stroking and has been implicated in the coding of pleasant touch are specifically affected in HSAN III patients. We addressed the relationship between C-tactile afferent function and pleasant touch perception in 15 patients with HSAN III and 15 age-matched control subjects. A soft make-up brush was used to apply stroking stimuli to the forearm and lateral aspect of the leg at five velocities: 0.3, 1, 3, 10 and 30 cm/s. As demonstrated previously, the control subjects rated the slowest and highest velocities as less pleasant than those applied at 1-10 cm/s, which fits with the optimal velocities for exciting C-tactile afferents. Conversely, for the patients, ratings of pleasantness did not fit the profile for C-tactile afferents. Patients either rated the higher velocities as more pleasant than the slow velocities, with the slowest velocities being rated unpleasant, or rated all velocities equally pleasant. We interpret this to reflect absent or reduced C-tactile afferent density in the skin of patients with HSAN III, who are likely using tactile cues (i.e. myelinated afferents) to rate pleasantness of stroking or are attributing pleasantness to this type of stimulus irrespective of velocity.

Psychiatric symptoms of patients with primary mitochondrial DNA disorders.

BACKGROUND: The aim of our study was to assess psychiatric symptoms in patients with genetically proven primary mutation of the mitochondrial DNA. METHODS: 19 adults with known mitochondrial mutation (MT) have been assessed with the Stanford Health Assessment Questionnaire 20-item Disability Index (HAQ-DI), the Symptom Check List-90-Revised (SCL-90-R), the Beck Depression Inventory-Short Form (BDI-SF), the Hamilton Depression Rating Scale (HDRS) and the clinical version of the Structured Clinical Interview for the the DSM-IV (SCID-I and SCID-II) As control, 10 patients with hereditary sensorimotor neuropathy (HN), harboring the peripheral myelin protein-22 (PMP22) mutation were examined with the same tools. RESULTS: The two groups did not differ significantly in gender, age or education. Mean HAQ-DI score was 0.82 in the MT (range: 0-1.625) and 0.71 in the HN group (range: 0-1.625). Level of disability between the two groups did not differ significantly (p = 0.6076). MT patients scored significantly higher on the BDI-SF and HDRS than HN patients (12.85 versus 4.40, p = 0.031, and 15.62 vs 7.30, p = 0.043, respectively). The Global Severity Index (GSI) of SCL-90-R also showed significant difference (1.44 vs 0.46, p = 0.013) as well as the subscales except for somatization. SCID-I interview yielded a variety of mood disorders in both groups. Eight MT patient (42%) had past, 6 (31%) had current, 5 (26%) had both past and current psychiatric diagnosis, yielding a lifetime prevalence of 9/19 (47%) in the MT group. In the HN group, 3 patients had both past and current diagnosis showing a lifetime prevalence of 3/10 (30%) in this group. SCID-II detected personality disorder in 8 MT cases (42%), yielding 3 avoidant, 2 obsessive-compulsive and 3 personality disorder not otherwise specified (NOS) diagnosis. No personality disorder was identified in the HN group. CONCLUSIONS: Clinicians should be aware of the high prevalence of psychiatric symptoms in patients with mitochondrial mutation which has both etiologic and therapeutic relevance.

[Treatment of patients with neuromuscular disease in a warm climate]. / Behandling i varmt klima for pasienter med nevromuskulaere sykdommer.

BACKGROUND: Several patient groups request treatment in a warm climate, in spite of the fact that the effects of such treatment are undocumented. MATERIAL AND METHODS: 47 children and 40 adults with neuromuscular diseases were recruited, stratified according to sex, use or non-use of electric wheelchair, primary myopathy or hereditary neuropathy, and randomised into two adult and two children groups. The patients were treated in a rehabilitation centre, either on Lanzarote or in Norway. All patients were monitored with physical tests and questionnaires at the start of the study, at the end of the treatment period, after three months (all groups) and after six months (adults only). RESULTS: No significant differences in effect between the groups were found. In the warm climate, the adult patient group showed a statistically significant improvement regarding pain, quality of life, depression, and results of physical tests at the end of treatment. After three months, the improvement in physical tests was still present. Among adult patients treated in Norway, improvement in physical tests was statistically significant after three months, but not at the end of the treatment period. INTERPRETATION: This study did not show a statistically significant difference between patients with various neuromuscular diseases treated in a warm climate compared to similar patients treated in Norway.

Profiles of neuromuscular diseases. Hereditary motor and sensory neuropathy, types I and II.

Data were collected prospectively for an impairment and disability profile for 86 hereditary motor and sensory neuropathy, types I and II (HMSN) subjects over a 10-yr period. Our data confirm that HMSN is a slowly progressive disorder that has a very heterogeneous phenotypical expression. The disorder was characterized primarily by diffuse muscle weakness with prominent distal atrophy. The mean manual muscle test (MMT) strength grade for all muscle groups combined was 3.9 +/- 0.7 MMT units. There was a slowly progressive decline in strength, only -0.15 MMT units per decade. Distal muscle groups were weaker than proximal muscles, and the decline in strength of the ankle muscles was greater than for the proximal muscles. There was no side dominance. Anthropometric data revealed that distal atrophy may be masked by subcutaneous fat in female subjects. On average, HMSN subjects produced 20-40% less force than normal controls, using quantitative isometric and isokinetic strength measures, even when MMT scores were normal. Pulmonary and cardiac abnormalities were uncommon, as were spine deformity and joint contractures. Only 1 individual had severe restrictive lung disease, and 12 (14%) had a history of significant respiratory complications with no age or disease duration effect. As with the other neuromuscular diseases, maximum expiratory pressure was more affected than forced vital capacity. Fourteen individuals (30%) had abnormal electrocardiograms, and six (7%) had a history of significant cardiovascular complications with no age or disease duration effect. Kyphosis was the major spine deformity. Cardiopulmonary responses to exercise testing were markedly abnormal, showing reduced aerobic capacity. Functional evaluations and timed motor performance tests showed only mild disability in most individuals. With timed motor performance testing muscle weakness translated to impaired motor performance skills. Overall, mean scores on intellectual function and neuropsychologic profiles were normal.