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1.
This report summarizes what we believe to be the first verifiable case of a significant and progressive motor neuron disease (MND) consistent with amyotrophic lateral sclerosis that resolved during treatment with i.v. ceftriaxone plus oral atovaquone and mefloquine. The rationale for use of these antibiotics was (i) positive testing for Borrelia burgdorferi and (ii) red blood cell ring forms consistent with Babesia species infection. The patient has continued to be free of MND signs and symptoms for 15 months, although some symptoms consistent with disseminated Borreliosis remain.  相似文献   
2.
OBJECTIVE: This study investigated whether aminophylline has an acute effect on the muscle performance of patients with amyotrophic lateral sclerosis (ALS). The study was a randomized, double-blind, crossover against placebo. MATERIALS AND METHODS: Twenty-five patients (48.5 +/- 14.1 years) with ALS were evaluated by means of forced vital capacity (FVC), maximal mouth inspiratory and expiratory pressures (P(Imax)/P(Emax)) and endurance, maximum voluntary ventilation (MVV) and handgrip strength (HS); variables were measured before and after the patients received an intravenous infusion of aminophylline or placebo. RESULTS: MVV (P<0.02) and HS of the right and left hands (P=0.05) increased after aminophylline infusion. There was a positive correlation between FVC and P(Imax) (r=0.80; P<0.05); between MVV and P(Imax) post-aminophylline, respectively (r=0.77; P<0.05). Serum aminophylline levels ranged from 5.3 to 10.5 microg/mL (mean 7.30). CONCLUSION: The acute administration of aminophylline improves the endurance of respiratory muscles and increases handgrip strength in patients with ALS.  相似文献   
3.
OBJECTIVE: This case-control study explored the possibility of an association between body mass index (BMI) and meralgia paresthetica (MP). PATIENTS AND METHODS: A total of 104 MP cases (33 women and 71 men, mean age 51.7 +/- 15.5 years) were matched for age and sex with 208 neurological and 208 dermatological controls. Differences between cases and controls were analyzed using the Wilcoxon and chi-squared tests. Odds ratio matched K controls (OR(MK)) and 95% confidence intervals (CI) were also calculated. RESULTS: Mean BMIs were 28.0 +/- 4.9 for cases and 26.0 +/- 4.3 and 25.5 +/- 3.9 for neurological and dermatological controls, respectively. There were significant differences between absolute BMI of cases and neurological (P < 0.01) as well as dermatological controls (P < 0.001), and also significant associations between BMI categories and MP (P = 0.008 vs neurological controls and P = 0.004 vs dermatological controls). There were significant OR(MK) for obesity (BMI >or= 30) [OR(MK) vs neurological controls 2.04 (95% CI 1.13-3.67) and vs dermatological controls 2.5 (95% CI 1.4-4.5)]. CONCLUSION: High BMIs were associated with MP. Obesity doubled the risk of MP. MP may be related to increased pressure due to abdominal protrusion.  相似文献   
4.
Little information is available regarding the morphological changes in the mitochondria in amyotrophic lateral sclerosis (ALS). In particular, mitochondrial changes in dorsal root ganglion cells have not yet been examined. We therefore conducted an electron microscopic examination of the mitochondria in dorsal root ganglion cells in 11 sporadic ALS patients, and 12 age-matched, non-neurological control individuals in order to determine whether or not they are affected in ALS. In both the controls and ALS patients, unusual inclusion bodies were frequently observed in the mitochondria in the somata of the ganglion cells. The inclusions consisted of an aggregate of tubules measuring approximately 40 nm in diameter varying in size and number. Such inclusions were frequently present in the cristae and/or intermembrane space, often expanding to form large bundles in the dilated intermembrane space. These structures quite frequently protruded outward unilaterally or bilaterally and were partially surrounded by the outer membrane of the mitochondria. The number of inclusions was significantly higher in the ALS patients than in the controls (P < 0.0001). Regularly spaced transverse processes similar to the rungs of a ladder were occasionally observed in the intermembrane space, along with infrequent but markedly increased cristae and stubby mitochondria. We concluded that mitochondrial abnormalities may be involved in the degenerative processes in the dorsal root ganglion cells in sporadic ALS. These findings therefore suggest that ALS is a widespread, more generalized disorder than previously thought, and that the degeneration is not confined to the motor neuron system.  相似文献   
5.
Recently, 43-kDa TAR DNA-binding protein (TDP-43) was identified as a component of ubiquitinated inclusions (UIs) in sporadic amyotrophic lateral sclerosis (SALS). To clarify whether TDP-43 immunoreactivity is present in neuronal inclusions in familial ALS (FALS), we examined immunohistochemically the brains and spinal cords from four cases of FALS, two with Cu/Zn superoxide dismutase (SOD1) gene mutation and two without, together with three cases of SALS and three control subjects, using two antibodies, one polyclonal and one monoclonal, against TDP-43. Neuropathologically, the SOD1-related FALS cases were characterized by Lewy body-like hyaline inclusions (LBHIs) in the lower motor neurons. On the other hand, the SOD1-unrelated FALS cases showed degeneration restricted to the upper and lower motor neuron systems, with Bunina bodies (BBs) and UIs in the lower motor neurons, being indistinguishable from SALS. No cytoplasmic TDP-43 immunoreactivity was observed in the control subjects or SOD1-related FALS cases; LBHIs were ubiquitinated, but negative for TDP-43. UIs observed in the SALS and SOD1-unrelated FALS cases were clearly positive for TDP-43. BBs were negative for this protein. Interestingly, in these SALS and FALS cases, glial cells were also found to have cytoplasmic TDP-43-positive inclusions. These findings indicate that the histological and molecular pathology of SALS can occur as a phenotype of FALS without SOD1 mutation.  相似文献   
6.
7.
The rapid confirmation of the initial report by Neumann et al. (Science 314:130–133, 2006) that transactive response (TAR)-DNA-binding protein 43 (TDP-43) is the major disease protein linking frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) with and without motor neuron disease (MND) as well as amyotrophic lateral sclerosis (ALS) implies that TDP-43 proteinopathy underlies major forms of sporadic as well as familial FTLD and ALS. Not only was the identity of the ubiquitinated proteins that accumulate in neurons and glia of these disorders finally resolved, but it also was shown that pathologic TDP-43 was hyperphosphorylated, ubiquitinated and cleaved to generate C-terminal fragments in affected brain and spinal cord of FTLD-U and ALS. This review summarizes the growing evidence that TDP-43 proteinopathy is the common pathologic substrate linking FTLD and ALS, and it considers the implications of these findings for developing better strategies to diagnose and treat these neurodegenerative disorders.  相似文献   
8.
We describe a new family with adult onset amyotrophic lateral sclerosis (FALS), in which the disease was characterized clinically by relatively rapid progression of bulbar symptoms. Gene analysis of Cu/Zn superoxide dismutase (SOD1) performed in one patient showed no mutations. Autopsy of another patient demonstrated degenerative changes restricted to the upper and lower motor neuron systems; no evident changes were observed in the posterior column, Clarke’s column or spinocerebellar tracts. The presence of Bunina bodies and ubiquitin-positive skein-like inclusions in the lower motor neuron was of considerable interest. Cases of FALS with such pathological features are quite rare in the literature. Identification of the gene responsible for the disease is desirable in order to shed further light on the molecular pathology of not only familial, but also sporadic, ALS.  相似文献   
9.
The presence of many neurofibrillary tangles (NFTs) in the central nervous system is a hallmark of amyotrophic lateral sclerosis (ALS) and parkinsonism–dementia complex (PDC) in people living in the Kii peninsula of Japan and in the island of Guam. To determine whether or not ALS and PDC are on a spectrum of a single tauopathy, we investigated the topography of NFTs semiquantitatively in two patients with ALS, three with PDC, and two with “PDC plus ALS” (PDC followed by ALS) on the basis of clinical symptoms. NFTs were counted under ×100 magnification of Gallyas-Braak stained preparations and were plotted on brain maps of the hemisphere, brainstem, and the spinal cord. In all cases, the hippocampus, particularly in the CA1 field, the parahippocampal gyrus, amygdaloid nucleus, and the temporal poles were most severely affected. In the neocortex, layers II–III were more severely affected by NFTs than layers V–VI. In the spinal cord, a few NFTs were revealed in the intermediate gray. NFTs were dense in all cases of PDC and “PDC plus ALS” and variable in density in ALS cases, although the topography was similar between them. We conclude that similar topographical distribution of NFTs in ALS and PDC in people living in the Kii peninsula of Japan suggests a single tauopathy.  相似文献   
10.
TDP-43 in differential diagnosis of motor neuron disorders   总被引:15,自引:13,他引:2  
Motor neuron disorders are clinically and pathologically heterogeneous. They can be classified into those that affect primarily upper motor neurons, lower motor neurons or both. The most common disorder to affect both upper and lower motor neurons is amyotrophic lateral sclerosis (ALS). Some forms of motor neuron disease (MND) affect primarily motor neurons in the spinal cord or brainstem, while others affect motor neurons at all levels of the neuraxis. A number of genetic loci have been identified for the various motor neuron disorders. Several of the MND genes encode for proteins important for cytoskeletal stability and axoplasmic transport. Despite these genetic advances, the relationship of the various motor neuron disorders to each other is unclear. Except for rare familial forms of ALS associated with mutations in superoxide dismutase type 1 (SOD1), which are associated with neuronal inclusions that contain SOD1, specific molecular or cellular markers that differentiate ALS from other motor neuron disorders have not been available. Recently, the TAR DNA binding protein 43 (TDP-43) has been shown to be present in neuronal inclusions in ALS, and it has been suggested that TDP-43 may be a specific marker for ALS. This pilot study aimed to determine the value of TDP-43 in the differential diagnosis of MND. Immunohistochemistry for TDP-43 was used to detect neuronal inclusions in the medulla of disorders affecting upper motor neurons, lower motor neurons or both. Medullary motor neuron pathology also was assessed in frontotemporal lobar degeneration (FTLD) that had no evidence of MND. TDP-43 immunoreactivity was detected in the hypoglossal nucleus in all cases of ALS, all cases of FTLD-MND and some of cases of primary lateral sclerosis (PLS). It was not detected in FTLD-PLS. Surprisingly, sparse TDP-43 immunoreactivity was detected in motor neurons in about 10% of FTLD that did not have clinical or pathologic features of MND. The results suggest that TDP-43 immunoreactivity is useful in differentiating FTLD-MND and ALS from other disorders associated with upper or lower motor neuron pathology. It also reveals subclinical MND in a subset of cases of FTLD without clinical or pathologic evidence of MND.  相似文献   
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