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Dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder characterized by slowly progressive cerebellar ataxia. Previously, autonomic symptoms or dysfunction have not been reported. To evaluate subclinical autonomic dysfunction regarding thermoregulatory function in SCA, we recorded sympathetic outflow to skin in a DRPLA patient confirmed by genetic analysis. We recorded skin sympathetic nerve activity (SSNA), which was elicited and recorded by using the microneurographical technique. In results, the resting frequency of SSNA bursts was very low (8.2 ± 0.4 bursts/min [institutional normal range: 20.8 ± 2.4 bursts/min]). However, acceleration of SSNA bursts induced by mental arithmetic stress was confirmed. The amplitude of reflex bursts induced by electrical stimuli was slightly low (9.6 ± 1.6 μV [institutional normal range: 10.9 ± 2.2 μV]), and the reflex latency was mildly prolonged (872 ± 23.7 msec [institutional normal range: 761.9 ± 51.7 msec]). These results suggest potentially central autonomic dysfunction in this patient with DRPLA. To our knowledge, this is the first report to record SSNA and confirm subclinical autonomic dysfunction in a case with DRPLA.

This study evaluated yearly changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rates (HR) for patients with Parkinson's disease (PD). Data were collected for the last 10 years from medical records of 28 PD patients and 30 non-PD patients with other neurological disorders. Age-related changes in each group were analyzed by year using mean values of SBP, DBP, and HR obtained at their bi-monthly visits. In results, PD patients had a gradual decrease in SBP with longer disease duration, and mean SBP significantly decreased from Year 7-11 compared to the mean values for Year 1 (p < .001 or p < .01). In non-PD patients, mean SBP significantly increased from Year 4-11 compared to the mean values for Year 1 (p < .001 or p < .01). This is the first study to report age-related changes of BP in individual patients with PD over 10 years.

We report a case of neuronal intranuclear inclusion disease (NIID) confirmed by detection of intranuclear inclusions in a skin biopsy specimen. Brain magnetic resonance imaging showed mild cerebral atrophy and linear hyperintensities at the corticomedullary junction on diffusion-weighted images. This patient developed nonconvulsive status epilepticus with generalized periodic discharges on electroencephalography after recurrent symptoms of paroxysmal nausea and slowly progressive cognitive decline. There have been no previous reports of NIID with nonconvulsive status epilepticus to our knowledge. Since adult patients with NIID display a wide variety of clinical manifestations, skin biopsy should be considered in patients who have leukoencephalopathy of unknown origin., Highlights • We report a case of neuronal intranuclear inclusion disease (NIID) confirmed by detection of intranuclear inclusions in a skin biopsy specimen. • This patient developed non-convulsive status epilepticus with generalized periodic discharge on electroencephalography. • Since adult patients with neuronal NIID display a wide variety of clinical manifestations, skin biopsy should be recommended in patients who have leukoencephalopathy of unknown origin.

A 35-year-old male was admitted to our hospital because of suspected myelitis. T2-weighted spinal MRI revealed a high intensity area at Th7-9. On admission, he showed mild weakness of the lower extremities and hyperreflexia of all extremities. Therefore, he was diagnosed with having spastic paraplegia. He presented no trismus or opisthotonos. There was pleocytosis in the cerebral spinal fluid. Dysuria, constipation and spasticity of the bilateral legs worsened, even though we administered methylprednisolone pulse therapy. Nonetheless, the symptoms had progressed on the 11th hospital day, opisthotonus and optic hyperesthesia were presented. On the 13th hospital day, we suspected local tetanus and administered tetanus toxoid. After one month, his symptoms had gradually improved. In the case of spastic paraplegia showing a subacute progression course and a faint abnormality on spinal MRI, the possibility of local tetanus should be considered.

To find out the physiological method for evaluating the severity of central autonomic dysfunction, we performed detailed evaluation of cutaneous vasomotor neural function in a comparatively large sample of multiple system atrophy (MSA). We evaluated cutaneous vasomotor neural function in 24 MSA patients. Skin sympathetic nerve activity (SSNA) and sympathetic skin response (SSR) and skin blood flow (skin vasomotor reflex [SVR]) were recorded at rest, as well as reflex changes after electrical stimulation. The parameters investigated were SSNA frequency at rest, reflex latency and amplitude of SSNA reflex bursts, absolute decrease and percent reduction of SVR, recovery time, and spontaneous SVR and SSR frequency. There were negative correlations between resting SSNA and disease duration or the SCOPA-AUT score, but these were not significant. SSNA reflex latency displayed significant positive correlations with disease duration and SCOPA-AUT score (p

Background Non-dystrophic myotonias (NDMs) are skeletal muscle disorders involving myotonia distinct from myotonic dystrophy. It has been reported that the muscle pathology is usually normal or comprises mild myopathic changes in NDMs. We describe various pathological findings mimicking those of myotonic dystrophy (DM) in biopsied muscle specimens from a patient with NDMs with a long disease duration. Case presentation A 66-year-old Japanease man presented eye closure myotonia, percussion myotonia and grip myotonia together with the warm-up phenomenon and cold aggravation from early childhood. On genetic analysis, a heterozygous mutation of the SCN4A gene (c.2065 C > T, p.L689F), with no mutation of the CLCN1, DMPK, or ZNF9/CNBP gene, was detected. He was diagnosed as having NDMs. A biopsy of the biceps brachii muscle showed increasing fiber size variation, internal nuclei, chained nuclei, necrotic fibers, fiber splitting, endomysial fibrosis, pyknotic nuclear clumps and disorganized intermyofibrillar networks. Sarcoplasmic masses, tubular aggregates and ragged-red fibers were absent. Conclusion It is noteworthy that the present study revealed various pathological findings resembling those seen in DM, although the pathology is usually normal or mild in NDMs. The pathological similarities may be due to muscular modification with long-standing myotonia or excessive muscle contraction based on abnormal channel activity. Electronic supplementary material The online version of this article (10.1186/s12883-019-1360-0) contains supplementary material, which is available to authorized users.

Creutzfeldt-Jakob disease (CJD) presents with rapidly progressive dementia associated with several symptoms including pyramidal, extrapyramidal, and cerebellar signs. In Japan, patients with PRNP gene mutations comprise 18.3% of CJD cases. In the present study, we report a 74-year-old man with a double mutation in the PRNP gene. He showed dysarthria, gait disturbance, and cognitive impairment. High signal intensity was observed in the bilateral cortex on brain MRI in diffusion-weighted images. There were high total Tau protein and 14-3-3 protein levels in the cerebrospinal fluid. We diagnosed him as having CJD clinically, and analyzed the PRNP gene, which revealed a V180I mutation and a M232R one, i.e., a compound heterozygous status. In our patient, the disease has very slowly progressive (total disease course, 37 months). The V180I and M232R mutations are specific mutations to Japanese CJD patients. For patients with a double PRNP gene mutation, only V180I and M232R have been known. Patients with a double mutation (V180I /M232R) in the PRNP gene might show an atypical disease course with a slow progression.

A 33-year-old woman was admitted due to disturbance of consciousness, dysarthria, dysphagia, sensory disturbances and weakness of the left upper limb after mycoplasma infection. She was treated with intravenous immunoglobulin and intravenous high-dose methylprednisolone as Bickerstaff brainstem encephalitis (BBE). On the 15th hospital day, reflex myoclonus appeared on her face, neck, body and limbs induced by techniques of jaw jerk reflex and patellar tendon reflex. The myoclonus was disappeared after two weeks in accordance with improvement of BBE. The transient reflex myoclonus may be originated from brainstem lesion which was affected by BBE. Reflex myoclonus is thought to be rare symptom in patient with BBE.

The detailed pathophysiology of limb coldness in multiple system atrophy (MSA) is unknown.We evaluated cutaneous vasomotor neural function in 18 MSA patients with or without limb coldness, and in 20 healthy volunteers as controls. We measured resting skin sympathetic nerve activity (SSNA) and spontaneous changes of the sympathetic skin response (SSR) and skin blood flow (skin vasomotor reflex: SVR), as well as SVR and reflex changes of SSNA after electrical stimulation. The parameters investigated were the SSNA frequency at rest, amplitude of SSNA reflex bursts, absolute decrease and percent reduction of SVR, recovery time, and skin blood flow velocity.Both the resting frequency of SSNA and the amplitude of SSNA reflex bursts were significantly lower in the MSA group than the control group (p0.001 and p0.05, respectively). There were no significant differences between the two groups with regard to the absolute decrease or percent reduction of SVR volume. The recovery time showed no significant difference between all MSA patients and control groups, but it was significantly prolonged in six MSA patients with limb coldness compared with that in the control group and that in MSA patients without limb coldness (p0.01). The skin blood flow velocity was significantly slower in the MSA group than in the control group (p0.001).In MSA patients, limb coldness might occur due to impairments of the peripheral circulation based on prolongation of vasoconstriction and a decrease of skin blood flow velocity secondary to combined pre- and postganglionic skin vasomotor dysfunction.

To investigate the vasomotor regulation in multiple system atrophy (MSA), we simultaneously recorded muscle sympathetic nerve activity (MSNA), heart rate, and blood pressure in 14 MSA patients without syncope and 18 healthy subjects. Resting MSNA bursts were significantly less frequent in MSA patients than healthy subjects (p

We recorded skin sympathetic nerve activity (SSNA), SSR, and SVR in 30 subjects. SSNA and SVR showed a slight decrease and spontaneous changes in resting SSR were significantly less frequent in older subjects compared with younger subjects (p

Metronidazole-induced encephalopathy (MIE) is a rare clinical condition resulting from long-term use of metronidazole. The symptoms and brain MRI changes in MIE usually resolve dramatically on discontinuation of treatment, and thus MIE with brain cystic lesions has rarely been reported. A 49-year-old woman was treated for a lumbar abscess with oral administration of 1.5 g/day of metronidazole for 4 months. Neurological examination revealed aphasia, apraxia, agraphia, cerebellar ataxia, and cognitive impairment. On brain MRI, diffusion-weighted imaging and the apparent diffusion coefficients were consistent with cytotoxic edema in the corpus callosum and subcortical white matter, representing delayed huge cystic lesions. Thus, we should be aware of MIE with irreversible brain lesions.

To unravel the pathogenesis of cold limbs in Parkinson’s disease, we evaluated cutaneous vasomotor neural function in 25 Parkinson’s disease patients with or without cold limbs and 20 healthy controls. We measured resting skin sympathetic nerve activity, as well as reflex changes of skin blood flow and skin sympathetic nerve activity after electrical stimulation, with the parameters including skin sympathetic nerve activity frequency at rest, the amplitude of reflex bursts, the absolute decrease and percent reduction of blood flow, and the recovery time which was calculated as the interval from the start of blood flow reduction until the return to baseline cutaneous blood flow. The resting frequency of skin sympathetic nerve activity was significantly lower in patients with Parkinson’s disease than in controls (p

A 29-year-old man developed muscle weakness in the neck at age 27. An increasing serum creatine kinase (CK) activity was detected. The first examination at our hospital revealed severe muscular atrophy at the front of the neck. Subsequently, muscular atrophy and weakness developed in the shoulders and upper extremities with an increasing serum CK level, which reached 9,159 IU/l. Needle electromyography (EMG) was not able to reveal typical myopathic change represented low-amplitude motor unit potentials (MUPs) in the proximal parts of the upper and lower extremities at the first examination, but in the course of the disease, the MUPs amplitude decrease in the same muscles. Serum examination gave a positive result for anti-signal recognition particle (SRP) antibodies. A biopsy of the deltoid muscle revealed necrotizing myopathy including small angular fiber-like atrophy without inflammatory cell infiltration or fibrotic proliferation. He was treated with prednisolone and tacrolimus with the diagnosis of polymyositis. The characteristic feature in this patient is that muscular atrophy and weakness were mainly observed in the neck. Moreover, the neurogenic changes on EMG in the early stage are also observed on atypical. Polymyositis with anti-SRP antibodies has the distinctive feature of typical polymyositis with cellular infiltration clinically and pathologically. In this respect, this case has striking and suggestive features of polymyositis with anti-SRP antibodies.

In patients with amyotrophic lateral sclerosis (ALS), sudomotor and vasomotor function have been considered to be impaired based on sympathetic skin response (SSR) or cutaneous blood flow measurements. We evaluated sympathetic sudomotor and vasoconstrictive neural function in ALS. We simultaneously recorded SSR, skin blood flow, and skin sympathetic nerve activity (SSNA) by microneurography in 20 patients with sporadic ALS and 20 healthy controls. Resting frequency of SSNA was significantly higher in ALS patients than in controls (p

We investigated the effects of edaravone, a free radical scavenger, on peripheral nerve ischemia-reperfusion injury caused by ligation of vessels supplying the sciatic and tibial nerves in rats. The control group was administered a placebo, the standard-dose group was given 3 mg/kg of edaravone intraperitoneally every 24 hours, and the low-dose group was given 1 mg/kg of edaravone. At 7 days after reperfusion, neurological and electrophysiological parameters were improved in the standard-dose group as compared with the control group. After 14 days, however, these differences were no longer observed. After 21 days, persistent edema and nerve fiber degeneration were noted in the standard-dose group, but not in the control or low-dose groups. Edaravone was effective during the early reperfusion period, but chronic inhibition of reactive oxygen species may be detrimental for nerve regeneration after ischemia-reperfusion injury. Further studies are necessary to confirm the long-term influence of edaravone.

The purpose of this study was to evaluate the clinical and pathological features in patients with progressive-type familial amyloidotic polyneuropathy (FAP) using autopsy and biopsy specimens. A proband is a 33-year-old man with FAP type I who developed motor, sensory and autonomic impairments with neuropathy, heart failure, and anorexia. Genetic findings of transthyretin (TTR) revealed G to A transition in codon 54 causing a rare mutation of TTR Lys54. He died of pneumonia and severe cardiac failure 4 years after onset. Autopsy showed heavy amyloid deposition in the heart, peripheral nerves, thyroid, skin, fat tissue, prostate and testis, moderate in the sympathetic nerve trunk, vagal nerve, celiac plexus, pelvic plexus, bladder, gastrointestinal tract, tongue, pancreas, lung, pituitary, blood vessel, gall bladder, adrenals and muscles, and free in the central nervous system, liver, kidney and spleen. Sural nerve biopsy in a sibling confirmed TTR amyloidosis immunohistochemically. Electronmicroscopic findings of amyloid fibrils were similar to that of FAP Met30. Immunoelectronmicroscopic findings indicated the relationship between amyloid fibrils or non-fibrillar structure and collagen fibers. The distribution of amyloid deposition, heavy in the heart and lacking in the kidney, is a characteristic feature and reflected severity of FAP with TTR Lys54.

In amyotrophic lateral sclerosis (ALS), not only impairment of motor neurons but also impairment of the autonomic nervous system has been demonstrated by previous physiological studies. Several investigators have reported a correlation between autonomic dysfunction and respiratory dysfunction in ALS. This study analyzed the relation between parameters of respiratory function and muscle sympathetic nerve activity (MSNA) in a large number of ALS patients.In 50 patients with ALS (mean age (SD): 62.1 (11.7) years), MSNA, heart rate (HR), and blood pressure (BP) were recorded simultaneously. The arterial oxygen content (PaO2), arterial carbon dioxide content (PaCO2), and forced vital capacity expressed as a percentage of the predicted value for healthy controls (%VC) were determined as parameters of respiratory function.There were no significant correlations between MSNA and PaO2, PaCO2, %VC, or the disability score. Analysis of chronological changes in 14 patients examined twice showed that the disability score and PaCO2 were significantly increased, and %VC was significantly more decreased at the second examination compared with the first examination (p0.01 and p0.05, respectively). In contrast, HR, BP, burst rate of MSNA, and age-adjusted MSNA exhibited no significant changes between the first and second examinations.These findings show that gradual deterioration of respiratory function in ALS patients is not associated with changes of quantitative MSNA parameters, which may suggest that abnormality of the autonomic nervous system is a primary feature of ALS.

Exome sequencing revealed a novel missense mutation (c.2152G>A, p.E713K) in the KIAA0196 gene in a Japanese patient with SPG8. To date, only 10 mutations in the KIAA0196 gene have been reported in the world. We describe the clinical and genetic findings in our patient with SPG8, which is a rare dominant hereditary spastic paraplegia. Notably, our patient showed mild upper limb ataxia, which is a relatively atypical symptom of SPG8. Thus, our patient showed a wide clinical spectrum of SPG8.

A 54-year-old man was admitted due to progressive gait disturbance and cognitive impairment. On MRI, a hyperintense region was observed in the periventricular white matter on FLAIR imaging, with Gd-enhancement in the choroid plexus and periventricular wall. Cerebrospinal fluid (CSF) examination showed marked abnormalities including a high white blood cell count (WBC, 360 cells/mm(3). 83% lymphocytes), an elevated protein level (1,416 mg/dl), a low glucose level (12 mg/dl), and elevated cryptococcal antigen with positive Indian ink staining. Cryptococcal ventriculitis was diagnosed. The patient was initially treated with liposomal amphotericin B, fluconazole, voriconazole, and flucytosine for 38 weeks, followed by administration of itraconazole and fluconazole with some improvement. The brain MRI after one month showed septum formation in the posterior horn, which was suggestive of ventriculitis. Although ventriculitis is rare, we should pay attention to the presence of ventriculitis due to cryptococcal infection in the central nervous system.

Neurodegenerative diseases generally have a slow, progressive course involving a great deal of suffering for patients. We need to be patient and tolerant when facing such a disease, and to this end we should develop an efficient system of multidisciplinary care, both physical and psychological. For home-health based care, a multidisciplinary approach to planning treatment is required, involving a team that includes a number of doctors and other healthcare professionals who are experts in different fields. For neurodegenerative diseases, the primary disciplines involved are medicine, nursing, physical and rehabilitation medicine, caregiving, and welfare etc.

To analyze the correlation between muscle sympathetic nerve activity (MSNA) and cardiac 123I-metaiodobenzylguanidine (MIBG) uptake in patients with Parkinson's disease (PD), we measured both parameters in 14 PD patients who were 51 to 82 years of age (mean, 63.1 ± 8.7 years). The duration of PD was 2 to 26 years, and the disability level (modified Hoehn and Yahr stage) ranged from 2.0 to 4.0 (mean, 3.2 ± 0.5). MSNA was recorded from the peroneal nerve fascicles using microneurographic methods, and then cardiac MIBG scintigraphy was performed within 1 month. We analyzed the correlation between the standardized MSNA, expressed as a percentage of the predicted value based on control subject data, and the heart-to-mediastinum ratio (H/M) or washout ratio (WR) from early and delayed MIBG images. The relationships between disease duration or disability and MSNA, the H/M ratio, or the WR were also analyzed. No significant correlations were found between MSNA and H/M ratio or WR. Although MSNA was inversely correlated with disease duration and with disability level, neither the H/M ratio nor the WR showed a significant correlation with disease duration or disability level. Because MSNA and MIBG abnormalities were not related, functional changes in addition to organic changes in cardiac sympathetic nerve endings may result in abnormal uptake of MIBG in Parkinson's disease. © 2005 Movement Disorder Society

In a 19-year-old patient with status epilepticus arising in the right parietal neocortex, unenhanced ictal MRI showed abnormalities mainly in the right cerebral cortex, contralateral cerebellum, and ipsilateral thalamus. The thalamus is considered a key site of functional abnormality in this patient.

Right cerebral and contralateral cerebellar hypermetabolism were observed on FDG PET in a 68-year-old woman with familial Creutzfeldt-Jakob disease (CJD) at an early stage before seizures occurred. The disease progressed with frequent seizures, myoclonus, and a startle reaction. In all past reports, FDG PET studies demonstrated hypometabolism in the cerebrum, cerebellum, and thalamus in patients with CJD. Focal hypermetabolism corresponding with epileptic foci is a common finding in ictal epilepsy patients, and hypometabolism is common in patients with myoclonus or the startle reaction. This finding may reflect a prodromal pathophysiology of epilepsy. Attention should be paid to the diagnosis of CJD while using FDG PET.

Opsoclonus-myoclonus syndrome (OMS) is well known as a paraneoplastic syndrome or as a parainfectious neurologic complication. However, OMS associated with a neurodegenerative disorder has not been described previously. A 48-year-old woman had been diagnosed as multiple system atrophy-parkinsonian type (MSA-P) based on the findings of dopamine non-responsive parkinsonism with autonomic failure and typical findings on magnetic resonance imaging 5 years ago. She exhibited recurrent asynchronous and arrhythmic myoclonic movements of the upper limbs and abdomen with a very short duration, and involuntary eye movements, which were repetitive, rapid, random, multidirectional, conjugate saccades of irregular amplitude and frequency at rest. Based on hematological and radiological findings, the diagnosis was advanced MSA-P associated with OMS. As far as we are aware, there have not been any previous reports of such a case. Electronic supplementary material The online version of this article (doi:10.1186/s40673-014-0015-6) contains supplementary material, which is available to authorized users.

Purpose To determine whether frontotemporal lobar degeneration (FTLD) is associated with similar cardiovascular autonomic dysfunction to that seen in amyotrophic lateral sclerosis (ALS), we compared cardiovascular parameters between ALS patients and patients with FTLD. Methods In ten patients with FTLD (mean age ± SD: 71.6 ± 4.6 years) and 12 patients with ALS (mean age ± SD: 71.4 ± 4.6 years), MSNA (using microneurography), heart rate (HR), and blood pressure (BP) were recorded simultaneously. Results MSNA was significantly higher in both groups of patients compared with the controls (p

Despite considerable interest, a pure vasodilator response by skin sympathetic nerve activity (SSNA) bursts in human limbs has not been observed in previous studies. In a patient with progressive nonfluent aphasia, SSNA, sympathetic skin response, and skin blood flow were simultaneously recorded at rest and during electrical stimulation. There was a very low frequency of SSNA bursts at rest, and when electrical stimulation was delivered, reflex bursts of SSNA were always observed followed by a sympathetic skin response and an increase in skin blood flow. The reflex latency of SSNA was slightly prolonged and the mean amplitude of reflex SSNA bursts was lower after electrical stimulation, compared with the responses in healthy controls. We report for the first time that the active vasodilator component of cutaneous sympathetic activity in limbs was recorded without any vasoconstrictor component in a patient with progressive aphasia.

Numerous attempts have been made to visualize the motor cortex and pyramidal tract lesions in patients with ALS using magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT) and positron emission tomography (PET). This paper briefly reviews the applicability of these imaging modalities in ALS. (ALS 2000; 1(suppl 2): S3-S6)

We report a 19-year-old Japanese man with a heterozygous deletion mutation (c.1485delA, p.G497AfsX527) in the fused in sarcoma/translated in liposarcoma gene. His mother and aunt were diagnosed with amyotrophic lateral sclerosis. He and his mother had learning disabilities. He noted muscle weakness of the right arm at age 18 years and 9 months. His respiratory function worsened rapidly, and he died of respiratory failure 11 months after onset. To date, the fused in sarcoma/translated in liposarcoma c.1485delA mutation has only been reported in three patients in a Caucasian family, and all those patients had a short disease course (12–18 months) and learning disabilities or slowness in school, similar to our patients. Thus, the fused in sarcoma/translated in liposarcoma c.1485delA mutation might cause a rapid disease course and affect the learning function. This is the first non-Caucasian patient with a heterozygous mutation, c.1485delA, in the fused in sarcoma/translated in liposarcoma gene.

A 77-year-old female developed vertigo and dysarthria. Two months later, she was hospitalized with disorientation and ataxia. CSF showed increased levels of NSE, 14-3-3 protein and tau. EEG demonstrated periodic synchronous discharges (PSD). Brain MRI showed abnormal high intensity areas in the cerebral cortices, especially in the occipital lobes, putamen and caudate nucleus bilaterally, on DWI. Genetical analysis of prion protein revealed no specific mutation. She was diagnosed as having sporadic Creutzfeldt-Jakob disease (CJD). Cheyne-Stokes respiration (CSR) had been observed since an early stage, and decreased 5 months later coincident with attenuation of myoclonus and PSD. We should also pay attention to CSR in the diagnosis of CJD, although the complication is rare.

A 49-year-old man subacutely developed muscle weakness in four extremities over a few days. He had no past or family history of muscle weakness. His blood tests showed significant hypokalemia without endocrinological abnormalities. With the diagnosis of hypokalemic myopathy, potassium was administered orally, and his symptoms improved. The patient had been drinking a beverage containing green tea extract too much two weeks before the symptoms developed, in addition to taking a cold remedy for ten years. Thus, hypokalemia is considered to be induced by the excessive intake of caffeine that accompanies the excessive consumption of the beverage and cold remedy.

There has been much progress in our understanding of transthyretin (TTR)-related amyloidosis including familial amyloidotic polyneuropathy (FAP), senile systemic amyloidosis and its related disorders from many clinical and experimental aspects. FAP is an inherited severe systemic amyloidosis caused by mutated TTR, and characterized by amyloid deposition mainly in the peripheral nervous system and the heart. Liver transplantation is the only available treatment for the disease. FAP is now recognized not to be a rare disease, and to have many variations based on genetical and biochemical variations of TTR. This chapter covers the recent advances in the clinical and pathological aspects of, and therapeutic approaches to FAP, and the trend as to the molecular pathogenesis of TTR.

Intramedullary tuberculoma with syringomyelia is rare. We treated a woman with back pain and weakness of the left leg that had slowly progressed for more than 30 years. Radiologic evaluation demonstrated a crescent-shaped calcification at the level of the C6 vertebra, and syringomyelia from C7 to T9. Laminectomy and syringosubdural shunt placement were performed, and a tuberculoma was removed. Back pain resolved after the operation, and mobility was facilitated. We recommend surgery for intrathecal tuberculoma with syringomyelia even when the course has been prolonged with no active tuberculous lesion.

Purpose Detection of hyperperfusion by I-123 N-isopropyl-p-iodoamphetamine single photon emission computed tomography can be helpful to diagnose dementia with Lewy bodies (DLB). This study characterized hypermetabolism in DLB. Materials and methods A total of 22 probable cases of DLB were examined by F-18 2-fluoro-2-deoxy-D-glucose positron emission tomography. Results Hypermetabolism was found in the peri-motor area, basal ganglia, and cerebellum. Eleven patients had hypermetabolism in all 3 areas, 6 in 2 areas, 4 in 1 area, and 1 in no area. Hypermetabolism was most frequent in the cerebellum. Comparison of the 11 patients with hypermetabolism in all 3 areas to the other 11 cases found no significant differences in age (P = 0.2555), sex (P = 0.1889), Mini-Mental State Examination score (P = 0.0897), and Parkinsonism. However, visual hallucinations were significantly more frequent in the patients with hypermetabolism in all 3 areas (P = 0.0018). Conclusions Hypermetabolism is common in patients with DLB and may be related to visual hallucinations.

Neuroferritinopathy is an autosomal dominant basal ganglia disease with iron accumulation caused by a mutation of the gene encoding ferritin light polypeptide (FTL). Six pathogenic mutations in the FTL gene have so far been reported. One such mutation was found in a Japanese family, thus suggesting that a new mutation in the FTL gene can therefore occur anywhere in the world. The typical clinical features of neuroferritinopathy are dystonia (especially orofacial dystonia related to speech and leading to dysarthrophonia) and involuntary movement, but such features vary greatly among the affected individuals. The findings of excess iron storage and cystic changes involving the globus pallidus and the putamen on brain MRI. and low serum ferritin levels are characteristic in neuroferritinopathy. Brain histochemistry shows abnormal aggregates of ferritin and iron throughout the central nervous system. Iron atoms are stored in the central cavity of the ferritin polymer and the E-helices of ferritin play an important role in maintaining the central cavity. A mutation in exon 4 of the FTL gene is known to alter the structure of E-helices, thereby leading to the release of free iron and excessive oxidative stress. Iron depletion therapy by iron chelation in symptomatic patients has not been shown to be beneficial, however before the nset of clinical symptoms, such a treatment strategy may still have some benefit. Neuroferritinopathy should therefore be considered in all patients presenting with basal ganglia disorders of unknown origin. These characteristic MRI findings may help to differentiate neuroferritinopathy from other diseases showing similar clinical features.

We encountered a 26-year-old Japanese woman with recurrent episodes of polymyalgia rheumatica-like symptoms associated with pregnancy. At a 13-week pregnancy, she was admitted to our outpatient clinic, complaining of myalgia on both thighs, shoulders and upper limbs. Laboratory examinations of blood yielded normal creatine kinase and mild elevation of erythrocyte sedimentation rate. After administration of oral prednisolone (10 mg/day) was begun, her symptoms were gradually resolved by 1 week. Further epidemiologic studies should be needed.

To confirm correlations between muscle sympathetic nerve activity (MSNA) and patients' chronological data, we selected 40 consecutive patients with sporadic amyotrophic lateral sclerosis (ALS) recorded by similar methods. MSNA at rest was quantified as the number of sympathetic bursts per 100 heartbeats and as the value expressed as a percentage of the predicted value based on control data. Twelve patients who underwent recordings of MSNA twice at intervals of 6 months or more showed marked decreases in MSNA amplitudes and frequencies between examinations. There was a slightly positive correlation between the frequency of MSNA and age, though younger patients exhibited higher values of MSNA than older patients. The standardized value of MSNA correlated negatively with disease duration and disability levels (p0.01, 0.05, respectively), but several patients with duration shorter than 12 months showed low values of MSNA. Twelve patients who underwent repeated recordings of MSNA showed a significant decrease in the mean standardized value of MSNA (102.6+/-24.9%) at the second examination, compared to the value (114.3+/-18.9%) at the first one. In ALS, sympathetic outflow to muscles tends to increase initially and then decrease with increasing age and duration. This pattern may be similar to chronological changes at motor neurons.

To confirm the diagnostic usefulness of muscle sympathetic nerve activity (MSNA) in differentiation between cervical spondylotic amyotrophy (CSA) and amyotrophic lateral sclerosis (ALS) with cervical spondylosis (CS), MSNA, heart rate (HR) and blood pressure (BP) were recorded in 10 patients with CSA and ALS with CS, and age-matched healthy volunteers at rest and during head-up tilting. There were no differences in age, disability scores, pulmonary function, and HR or BP at rest between ALS and CSA groups. Resting MSNA was significantly greater in patients with ALS with CS than in comparison groups (P

Background: Muscle sympathetic nerve activity (MSNA) at rest is widely known to increase with aging, but changes in skin sympathetic nerve activity (SSNA) with aging are less well defined. We examined the aging effects of reflex activities on SSNA, sympathetic skin response (SSR), and sympathetic flow response (SFR). Objective: We studied the aging effect of reflex activities on SSNA, SSR and SFR. Methods: SSNA, SSR and SFR were simultaneously recorded during randomly administered electrical stimuli. Results: The mean SSNA reflex latency was 763.1 ± 39.8 ms, mean SSNA amplitude was 12.6 ± 6.3 µV, mean SSR reflex latency was 1,809.0 ± 90.6 ms, mean SSR reflex amplitude was 0.519 ± 0.449 mV, mean SFR reflex latency was 4,398.9 ± 761.7 ms, and mean SFR reflex amplitude was 8.21 ± 5.14 ml/min/100 g. None of these parameters were significantly affected by aging. The reflex bursts on SSNA could be recorded in all subjects studied. While the frequencies of SSR and SFR were recorded in more than 80% of young subjects under age 40 years, the frequencies of SSR were recorded in less than 25% of subjects over age 80 years, and the frequencies of SFR were recorded in less than 5%. Conclusion: There were no differences in electrical stimuli-induced reflex SSNA between young and older subjects, but effector organ responses such as SSR and SFR were diminished in older subjects.

Histologic examination of sural nerve of a 32-year-old man with an aggressive polyneuropathy associated with autonomic failure demonstrated amyloid deposition, and familial amyloidotic polyneuropathy (FAP) was diagnosed. Immunohistochemical staining showed transthyretin (TTR) staining of the amyloid deposits in nerve. Sequencing revealed G to A transition in the codon 54 causing TTR Lys 54. This is a new variant TTR associated with aggressive FAP.