Bakgrund: Amyotrofisk lateralskleros, ALS, är en fortskridande motorneuronsjukdom som drabbar och bryter ner nervceller som styr skelettmuskulaturen. Sjukdomen orsakar stort lidande för patienter och kan vara snabbt fortskridande och oförutsägbar. Sjuksköterskor upplever att patienter med ALS behöver få adekvat information och stöd för att lindra lidande. Detta sker genom att sjuksköterskor är respektfulla och lyhörda på patientberättelsen. Närstående har också en stödjande funktion i patienters kamp mot sjukdomen genom att vara närvaro i vardagen. Syfte: Att beskriva patienters upplevelser av att leva med ALS.  Metod: En kvalitativ litteraturstudie baserad på tretton kvalitativa artiklar. Resultat: Två teman och fem subteman identifierades. Det första temat var en förändrad livssituation genom att uppleva rädsla för framtiden, att vara begränsad i vardagen och att vara beroende av omgivningen. Det andra temat var att anpassa sig till en ny tillvaro genom att leva med acceptans i nuet och att finna mening trots sjukdomen.  Slutsats: Patienter med ALS upplever en förändrad livssituation på grund av sjukdomen. Detta krävs en medvetenhet och kunskap om patienters upplevelser hos sjuksköterskor vilken kan bidra till bättre vård och öka anpassning för patienter i livet. Nyckelord: Kvalitativ, Motorneuronsjukdom, Palliativ vård, Patienters perspektiv, Upplevelser.

Spinal cord injuries and other neurological disorders can disturb the regulation of normal bladder function including continence and micturition. Developing new neuronal pathways by surgically rerouting nerves is a potential approach for restoring bladder function. Our laboratory successfully rerouted somatic nerves to the anterior vesical branch of the pelvic nerve to reinnervate the bladder muscle in canines. Electrical stimulation of these transferred nerves induced detrusor pressure and bladder emptying and we confirmed regrowth of these rerouted nerves using retrograde neurotracing methods. In these studies, reinnervation was proved at 1st and 3rd months after decentralization. We believe that our aim of developing an approach to surgically reinnervate the bladder after long-term decentralization is critical to the success of the reinnervation surgery due to the possibility that patients would delay having a surgery until they try other non-surgical approaches or therapies. We also demonstrated the reinnervation of urethral and anal sphincters by femoral to pudendal nerve transfer after sacral ventral root transection to restore continence. However, these studies did not demonstrate the reinnervation of bladder, urethra and anal sphincter, all in same animal that would be helpful to human patients with lower motor neuron lesioned bladders to restore both continence and emptying. Therefore, prior to applying these surgical procedures to human patients, further investigation is required to prove the effectiveness of nerve transfer strategies in this canine model using multiple experimental techniques. This dissertation is a part of a larger project in canines examining whether surgical rerouting of obturator to pelvic nerve and sciatic to pudendal nerve allows restoration of bladder, urethral and anal sphincter functions, including continence (storage) and emptying (voiding and defecation) functions, in lower motor neuron lesioned bladders. In this study, it was aimed to explore bladder and urethral reinnervation using behavioral observation and in-vivo electrophysiological techniques. In order to completely prove that the reinnervation surgeries are responsible for restoration of bladder and urethral functions, it was first necessary to demonstrate the absence of these functions in animals with long term decentralized bladders and to determine whether the same animals were able to recover functions after reinnervation. In specific aim 1, we addressed this goal by tracking squat-and-void behaviors at monthly intervals after decentralization and reinnervation, using home cage video recordings and evaluation of bladder sensation and emptying after bladder filling. Immediately prior to euthanasia, reinnervation was also explored by electrical stimulation of transferred nerves to evaluate motor function. Retrograde neuronal tracing was also performed to explore sensory reinnervation. Results showed evidence of functional restoration of bladder and urethral function in reinnervated animals based on behavior observation and electrical stimulation of transferred nerves. Also, regrowth of neuronal cells in the new neuronal pathways was observed that were developed by the nerve transfer surgeries. This study also aimed to establish an electroneurogram recording method (part of in-vivo electrophysiological experiments) to explore afferent (sensory) neuronal activity in transferred nerves induced by bladder filling. However, the extraction of neuronal activity from the peripheral nerves is a challenging task. Several factors including noise, interference from surrounding muscle activities and the electronic components can affect these microvolts level recordings. Choice of recording electrode in configuration with the whole recording setup also plays a significant role while performing these low amplitude signal recordings. In specific aim 2, we addressed this issue by refining electroneurogram recording techniques to obtain high strength signal during multifiber recording. We first developed custom electrodes, suitable for varying nerve diameters and available implantation sites, were tested for functionality. Then, we performed multiple testing using these electrodes with different amplifiers to calibrate noise in saline. Testing results helped to establish the recording setup suitable for in-vivo experimental environment. Later, these refined techniques were applied to record afferent (sensory) activity of sciatic nerves and afferent (sensory) and efferent (motor) activity of hypogastric nerves in rats. Based on the recording results, it was aimed to employ similar techniques in order to record nerve activity in the canine model. Prior to applying these refined techniques to explore sensory reinnervation from new neuronal pathways after nerve transfer surgeries, in specific aim 3, we aimed to assess the hypogastric nerve activity in normal intact and acutely lumbosacral decentralized bladders using these refined techniques. The effects of electrical stimulation of hypogastric nerves or lumbar roots on detrusor pressure were determined, as were effects of isoflurane versus propofol anesthetics on hypogastric nerve stimulation evoked pressure. Hypogastric nerve activity was recorded using custom-made bipolar cuff electrodes during bladder filling. To confirm or refute that any increase in electroneurogram during bladder filling is due to afferent activity from the end organ, the hypogastric nerve was transected between the recording electrode and the spinal cord and the effects of bladder filling on afferent but not efferent activity were recorded. Results showed that electrical stimulation of hypogastric nerves evoked low amplitude detrusor pressures that did not differ between the two anesthetics. Upper lumbar (L2) ventral root stimulation evoked detrusor pressures were suppressed, yet not eliminated after transection of hypogastric nerves and all spinal roots below L5. Afferent and efferent hypogastric nerve activity did not change with bladder filling in neuronally intact bladders but decreased in decentralized bladders. No change in afferent activity were observed during bladder filling in normal intact and decentralized bladders. Overall findings in this research indicate that the new neuronal pathways created by nerve transfer can restore bladder sensation and emptying function in lower motor neuron-lesioned canines. A more complete decentralized bladder model needs to include transection of both the lumbosacral spinal roots innervating the bladder and the hypogastric nerves prior to performing nerve transfer surgeries. The refined electroneurogram recording methods may be suitable for evaluating the effectiveness of nerve transfer surgeries by monitoring the sensory activities of the transferred nerve. / Electrical and Computer Engineering

No / Most research on partners' experiences of living with a person with MND is questionnaire-based with no qualitative study focusing on the period between diagnosis and end-of-life care. This study aimed to provide an in-depth qualitative exploration of the experience of living with, and caring for, a partner with MND. Semi-structured interviews were conducted with eight individuals, and transcripts analysed from an interpretative phenomenological perspective. Two main themes were derived. 'Impact on life' included having concern for partner's safety, having social restrictions, being continually tired, struggling with anger and frustration, loss of intimacy and uncertainty around the future; while 'Adjusting to the situation' included trying to be strong, retaining a sense of normality, appreciation of specialist services, adopting a problem-solving approach, living day to day and ability to remain positive. In conclusion, experiences of stress and loss are illustrated in this sample of partners of those with MND, and it is suggested both these aspects should be integrated into understanding of carers' experiences. Carers appear to inhibit their grief in order to appear strong. Greater understanding of the consequences of this would help in providing appropriate emotional support.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterised clinically by rapidly progressive paralysis leading ultimately to death from respiratory failure. There is no cure for ALS and no definitive explanation for the onset and rapid progression of motor neuron degeneration. Genetics is a known risk factor for a portion of familial cases. However, the role of genetics in the commoner sporadic form of the disease is poorly understood, although numerous genes have been implicated. The primary aim of this thesis project is to uncover the genetic causes that underlie ALS. To accomplish this goal, the main focus of this thesis is to perform genome-wide association analysis of sporadic ALS using high density SNP arrays. This thesis describes the first and the largest genome-wide association studies of ALS to date. Results demonstrate that there is no single large effect susceptibility variant underlying a large proportion of ALS, such as ApoE in Alzheimer’s disease. However, the genotyping data has been made publically available and the digital nature of this data means that it is a resource that can grow with future studies. Beyond genome-wide association, this thesis describes work using linkage, haplotype and sequence analysis to investigate the genetic overlap between ALS and frontotemporal dementia. Lastly, this thesis presents a novel method for linkage analysis using high throughput SNP arrays. Ultimately, it is hoped that by uncovering the genes that cause ALS, such knowledge will shed light on the pathogenic mechanisms underlying motor neuron degeneration and potentially lead to new rational therapies effective in slowing or even halting disease progression.

Title: The Use of Physiotherapy in Spasticity Management Objectives: The purpose of this thesis is to provide a summary of present findings on spasticity, with particular regard to its pathophysiological mechanisms and clinical manifestations, and to present an overview of medical and physiotherapeutic approaches applied in its treatment. Furthermore, it aims at making a research in physiotherapeutic methods and techniques used for reduction of spasticity. The thesis shall present relevant studies, provide their comparison and critically evaluate the effect of methods and techniques examined in them. Methods: This thesis is a descriptive analysis based on a literature review. Results: Based on the research findings, it may be concluded that physiotherapy has proven to be effective in reducing spasticity. However, it is not possible to determine whether the techniques to reduce spasticity are more effective than techniques without this primary purpose. The examined studies have shown that the choice of physiotherapeutic practices to reduce spasticity was not influenced by disease etiology. Moreover, the same techniques and methods were applied in pediatric and adult patients, regardless of diagnosis. The relationship between reduced spasticity and change in motor function is unclear and our research...

Introdução: A Esclerose Lateral Amiotrófica (ELA) é uma doença degenerativa e progressiva que afeta neurônios motores da medula espinhal, tronco cerebral e/ ou córtex motor. Sua manifestação clínica é bastante variada, sua etiologia desconhecida e a progressão, fatal. Não existe ainda um tratamento curativo para a ELA, porém alguns medicamentos e a realização de fisioterapia podem auxiliar, fornecendo ao paciente uma melhor qualidade de vida. Objetivos: Testar a hipótese de que técnicas quantitativas de Ressonância Magnética (RM) são eficazes para detectar a lesão neuronal no encéfalo de pacientes com ELA no estágio inicial da doença e, verificar se existe correlação entre a lesão encefálica e a perda funcional do paciente. Dessa forma, pretende-se estabelecer um protocolo capaz de contribuir para o diagnóstico precoce da ELA. Metodologia: Quinze pacientes com diagnóstico de ELA definida ou provável (12 homens e três mulheres), com idade entre 37 e 79 anos e seus respectivos controles foram submetidos a um protocolo de avaliação por RM, que incluiu um estudo estrutural volumétrico e quantitativo do dano neuronal e mielínico por razão de sequências ponderadas em T1 e FLAIR, da Transferência de Magnetização (MT), Relaxometria, Anisotropia Fracionada (FA) e Difusão (DTI), além da Espectroscopia de prótons. Alguns dos sujeitos foram submetidos também à uma avaliação física de força muscular, de funcionalidade através da Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R), de qualidade de vida através da Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) e de quantificação da fadiga pela Fadigue Severity Scale (FSS). Os dados da RM dos dois grupos foram comparados através da análise de variância multi e univariada e submetidos à correção de múltiplas comparações de Bonferroni. Nas variáveis com diferença significante entre os grupos, foi estudada a validade preditiva da medida, calculando-se a área sob a curva ROC e estabelecidos os valores de sensibilidade, especificidade e acurácia. Os dados das escalas foram comparados pelo teste de Mann-Whitney e correlacionados entre si e com as estruturas através da correlação de Spearman. Resultados: As várias técnicas da RM, com exceção da MT, identificaram pelo menos uma estrutura com diferença significante entre os dois grupos, totalizando 11 estruturas mais a razão dos metabólitos NAA/Cre. Os valores de sensibilidade, especificidade e acurácia foram satisfatórios variando entre 0,60 e 1,00 , com destaque para o Volume do Giro Superior Frontal Direito e Giro Superior Frontal Esquerdo que apresentaram valores 1,00 , 0,93 e 0,97 , respectivamente. As escalas ALSFRS-R e ALSAQ-40 apresentaram diferença significativa entre os dois grupos, mas a FSS não apresentou. As escalas apresentaram correlação significativa entre si em quase todos os escores totais e domínios. Já a correlação das escalas com as estruturas foi significativa apenas para o Volume. Conclusões: Técnicas como DTI, FA, Relaxometria e Volume se mostraram mais eficazes no diagnóstico precoce de pacientes com ELA do que as outras. A redução de volume de substância cinzenta se correlacionou positivamente com a ALSFRS-R. Por fim, propomos um protocolo para avaliação de pacientes com ELA, que inclua imagem volumétrica de alta resolução para cálculo da Volumetria e DTI. / Introduction: Amyotrophic Lateral Sclerosis (ALS) is a progressive and degenerative disease that affects motor neurons in the spinal cord, brain stem and/ or motor cortex. Their clinical presentation is varied, its unknown etiology and fatal progression. There isnt still a curative treatment for ALS, but some medications and physical therapy can help by providing the patient a better quality of life. Objectives: To test the hypothesis that quantitative techniques of magnetic resonance imaging (MRI) are effective to detect neuronal damage in the brain of patients with ALS at the inicial stage of the disease and see if there is a correlation between brain injury and functional loss of the patient. Thus, we intend to establish a protocol can to contribute to early diagnosis of ALS. Methods: Fifteen patients with definite or probable ALS (12 men and three women) aged between 37 and 79 and their respective controls underwent an MRI evaluation protocol, including a volumetric and quantitative structural study of damage neuronal and myelin by reason of T1-weighted sequences and FLAIR , Magnetization Transfer (MT), Relaxometry, Fractional Anisotropy (FA), Diffusion (DTI) and Proton magnetic resonance spectroscopy. Some of the subjects also underwent a physical assessment of muscle strength, functionality by Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R), quality of life through the Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) and quantification of fatigue by Fadigue Severity Scale (FSS). The MRI data of the two groups were compared using analysis of variance multivariate and univariate and submitted to correction for multiple comparisons of Bonferroni. In the variables with significant differences between groups, we studied the predictive validity of the measure, by calculating the area under the ROC curve and set the sensitivity, specificity and accuracy. The data of the scales were compared using Mann-Whitney test and correlated with each other and with the structures by Spearman correlation. Results: The various MRI techniques, with the exception of MT, identified at least one structure with a significant difference between the two groups, a total of 11 structures over the reason for the metabolites NAA/Cre. The sensitivity, specificity and accuracy were satisfactory ranging from 0.60 to 1.00 , with emphasis on Volume of Gyros Superior Frontal Right and Gyros Superior Frontal Left that averaged 1.00 , 0.93 and 0,97 , respectively. The ALSFRS-R and ALSAQ-40 scales showed significant differences between the two groups, but the FSS did not. The scales were significantly correlated with each other in almost all domains and total scores. The correlation with the structures of the scales was significant only for the Volume. Conclusions: Techniques such as DTI, FA, Relaxometry and Volume are more effective in early diagnosis of ALS patients than others. The decrease in gray matter volume was positively correlated with the ALSFRS-R. Finally, we propose a protocol for evaluation patients with ALS, including high-resolution volumetric image to calculate the Volume and DTI.

La sclérose latérale amyotrophique (SLA) est une pathologie neurodégénerative progressive se déclarant vers 50-60 ans. Elle est majoritairement de nature sporadique son incidence est estimée à 1 :1000. La SLA mène à une paralysie progressive et entraine généralement à la mort des patients de 2 à 5 ans suivant le diagnostic aux suite d’une fonte musculaire importante liée à la perte des neurones moteurs. Au cours des années, plusieurs mutations ont été identifiées autant chez les patients atteints de SLA sporadique que de SLA familiale. Ces mutations interfèrent avec la fonction de gènes variés, tels que DCTN1, codant pour la protéine dynactine1, sous-unité du complexe multimoléculaire dynactine. Ce complexe sert d’adaptateur au moteur moléculaire dynéine, chargé du transport axonal rétrograde, où sa fonction permettrait de régir l’activité du complexe moteur et sa capacité à lier divers cargos. Nous avons donc entrepris la caractérisation d’une lignée de poissons zèbre mutants pour dynactin1a (nommés mikre okom632, mokm632), plus particulière en terme du développement d’un type de neurone moteur primaire (les CaPs), afin de déterminer l’effet de la perte de fonction de ce gène sur l’axonogenèse, la formation et la stabilisation de la jonction neuromusculaire, sur le comportement de l’embryon, ainsi que sur le transport axonal.Nous suggérons que dynactin1 favorise la stabilité synaptique, où une perte de fonction de ce gène entraine des défauts de croissance, des anomalies éléctrophysiologiques et un comportement anormal. Ce rôle semble être indépendant des fonctions connues de régulateur du moteur dynéine. / Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease, which is mainly sporadic in nature. This progressive pathology has an estimated incidence of 1:1000 and generally leads to death within 2-5 years of diagnosis due to muscle wasting and severe motor neuron loss. Over the last years, mutations have been identified in both sporadic and familial ALS patients, interfering with the function of many genes, including DCTN1, which encodes for a subunit of the motor protein complex subunit dynactin. The dynactin complex serves as an adaptor for the dynein motor complex, responsible for retrograde axonal transport, and it is believed to regulate dynein activity and the binding capacity for cargos. We set out to characterize a mutant zebrafish line for dynactn1a (named mikre okom632, mokm632), looking specifically at caudal primary motor neurons (CaPs), with regard to axonal development, formation and stability of the neuromuscular junction (NMJ) and the behavioral phenotype produced in embryos, as well as axonal transport metrics. We suggest a role for dynactin1 in synapse stability, where the loss-of-function of this gene leads to growth defects, electrophysiological abnormalities and behavioral deficits. This role appears to be independent of its known function as a regulator of dynein, its implication in axonal transport, or its regulation of microtubule dynamics. With this study, we hope to elucidate key molecular mechanisms in ALS etiology by revealing the role of dynactin1 in NMJ development and maintenance.

Amyotrophic lateral sclerosis (ALS), also known as Charcot’s disease, motor neuron disease (MND) and Lou Gehrig’s disease, is a deadly, adult-onset neurodegenerative disorder characterized by progressive loss of upper and lower motor neurons, resulting in evolving paresis of the linked muscles. ALS is defined by classical features of the disease, but may present as a wide spectrum of phenotypes. About 10% of all ALS cases have been reported as familial, of which about 20% have been associated with mutations in the gene encoding for CuZn superoxide dismutase (SOD1). The remaining cases are regarded as sporadic. Research has advanced our understanding of the disease, but the cause is still unknown, no reliable diagnostic test exists, no cure has been found and the current therapies are unsatisfactory. Riluzole (Rilutek®) is the only registered drug for the treatment of ALS. The drug has shown only a modest effect in prolonging life and the mechanism of action of riluzole is not yet fully understood. ALS is diagnosed by excluding diseases with similar symptoms. At an early stage, there are numerous possible diseases that may present with similar symptoms, thereby making the diagnostic procedure cumbersome, extensive and time consuming with a significant risk of misdiagnosis. Biomarkers that can be developed into diagnostic test of ALS are therefore needed. The high number of unsuccessful attempts at finding a single diseasespecific marker, in combination with the complexity of the disease, indicates that a pattern of several markers is perhaps more likely to provide a diagnostic signature for ALS. Metabolomics, in combination with chemometrics, can be a useful tool with which to study human disease. Metabolomics can screen for small molecules in biofluids such as cerebrospinal fluid (CSF) and chemometrics can provide structure and tools in order to handle the types of data generated from metabolomics. In this thesis, ALS has been studied using a combination of metabolomics and chemometrics. Collection and storage of CSF in relation to metabolite stability have been extensively evaluated. Protocols for metabolomics on CSF samples have been proposed, used and evaluated. In addition, a new feature of data processing allowing new samples to be predicted into existing models has been tested, evaluated and used for metabolomics on blood and CSF. A panel of potential biomarkers has been generated for ALS and subtypes of ALS. An overall decrease in metabolite concentration was found for subjects with ALS compared to their matched controls. Glutamic acid was one of the metabolites found to be decreased in patients with ALS. A larger metabolic heterogeneity was detected among SALS cases compared to FALS. This was also reflected in models of SALS and FALS against their respective matched controls, where no significant difference from control was found for SALS while the FALS samples significantly differed from their matched controls. Significant deviating metabolic patterns were also found between ALS subjects carrying different mutations in the gene encoding SOD1.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by loss of motor neurons and their supporting cells in the brain, brainstem and spinal cord, resulting in muscle paresis and paralysis including the bulbar (speech, chewing, swallowing) and respiratory muscles. The average age at onset is 55 years, and death due to respiratory failure occurs 2-5 years after symptom onset in ~ 85% of cases. Five to 10% of ALS is familial, and about 20% of familial cases are associated with mutations in the superoxide dismutase 1 (SOD1) gene. To date, 118 SOD1 mutations have been reported worldwide (www alsod.org). All are dominantly inherited, except for the D90A mutation, which is typically recessively inherited. D90A homozygous ALS is associated with long (~14 years) survival, and some atypical symptoms and signs. The reason for this is not known. In contrast, most other SOD1 mutations are associated with average survival, while some are associated with aggressive disease having lower motor neuron predominance and survival less than 12 months. The A4V mutation, which is the most frequently occurring SOD1 mutation in the United States, is an example of the latter. Understanding the pathogenic mechanisms of SOD1 mutants causing widely different disease forms like D90A and A4V is of paramount importance. Overwhelming scientific evidence indicates that mutations in the SOD1 gene are cytotoxic by a “gain of noxious” function, which although not fully understood results in protein aggregation and loss of cell function. This thesis explores different ALS-SOD1 gene mutations in British Columbia (BC), Canada. Two hundred and fifty-three ALS patients were screened for SOD1 mutations, and 12 (4.7%) unrelated patients were found to carry one of 5 different SOD1 mutations: A4V (n=2); G72C (n=1); D76Y (n=1); D90A (n=2); and 113T (n=6). Incomplete penetrance was observed in 3/12 families. Bulbar onset disease was not observed in the SOD1 mutation carriers in this study, but gender distribution was similar to previously reported studies. Age at symptom onset for all patients enrolled, with or without SOD1 mutations, was older than reported in previous studies. On average, patients with SOD1 mutations experience a longer diagnostic delay (22.6 months) compared to patients without mutations (12 months). Two SOD1 patients were originally misdiagnosed including the G72C patient who’s presenting features resembled a proximal myopathy. Neuropathological examination of this patient failed to reveal upper motor neuron disease. The I113T mutation was associated with variable age of onset and survival time, and was found in 2 apparently sporadic cases. The D76Y mutation was also found in an apparently sporadic case. I113T and D76Y are likely influenced by other genetic or environmental factors in some individuals. Two patients were homozygous for the D90A mutation, with clinical features comparable to patients originally described in Scandinavia. Clinical and electrophysiological motor neuron abnormalities were observed in heterozygous relatives of one D90A homozygous patient. The A4V patients were similar to those described in previous studies, although one had significant upper motor neuron disease both clinically and neuropathologically. Clinical neurophysiology is essential in the diagnosis of ALS, and helpful in monitoring disease progression. A number of transcranial magnetic stimulation (TMS) studies may detect early dysfunction of upper motor neurons when imaging techniques lack sensitivity. Peristimulus time histograms (PSTHs), which assess corticospinal function via recording of voluntarily activated single motor units during low intensity TMS of the motor cortex, were used to study 19 ALS patients having 5 different SOD1 mutations (including 8 of the 12 patients identified with SOD1 mutations from BC). Results were compared with idiopathic ALS cases, patients with multiple sclerosis (MS), and healthy controls. Significant differences were found in corticospinal pathophysiology between ALS patients with SOD1 mutations, idiopathic ALS, and MS patients. In addition, different SOD1 mutants were associated with significantly different neurophysiologic abnormalities. D90A homozygous patients show preserved if not exaggerated cortical inhibition and slow central conduction, which may reflect the more benign disease course associated with this mutant. In contrast, A4V patients show cortical hyper-excitability and only slightly delayed central conduction. I113T patients display a spectrum of abnormalities. This suggests mutant specific SOD1 pathology(s) of the corticospinal pathways in ALS.

No description available.