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Ken Ohyama,
Haruki Koike,
Michihito Masuda,
Jun Sone,
Rina Hashimoto, Minoru Tomita,
Yuichi Kawagashira,
Masahiro Iijima,
Tomohiko Nakamura,
Hirohisa Watanabe,
Gen Sobue
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ABSTRACT: Acute sensory ataxic neuropathy (ASAN) is known to occur with acute and monophasic sensory ataxia. Although autonomic dysfunctions have been reported, no detailed descriptions are currently available. We describe a case of ASAN in which the autonomic manifestations were systematically investigated. Although the patient did not complain of any autonomic symptoms, except for photophobia due to mydriasis, autonomic testing revealed widespread autonomic dysfunctions. Norepinephrine and dobutamine infusion test indicated the presence of sympathetic dysfunction. Additionally, the pupillary response to pilocarpine revealed the presence of parasympathetic dysfunction. In conclusion, widespread, subclinical autonomic dysfunctions may be present in ASAN patients.
Autonomic neuroscience: basic & clinical 04/2013; · 1.82 Impact Factor
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ABSTRACT: IMPORTANCE The newly recognized entity IgG4-related disease (IgG4-RD) is characterized by an elevated IgG4 serum concentration and tissue infiltration by IgG4-positive plasma cells. We describe, for the first time, the clinical features and nerve biopsy findings of a patient with IgG4-RD who presented with neuropathy in the extremities. OBSERVATIONS A 55-year-old man had histopathologically defined IgG4-RD that manifested as sensory-motor neuropathy. The neuropathic features were multiple mononeuropathies with electrophysiological findings suggestive of axonal neuropathy. Marked thickening with abundant collagen fibers and infiltration of IgG4-positive plasma cells were observed in the epineurium of the biopsied sural nerve. A moderate degree of myelinated fiber loss without evidence of segmental demyelination was present, whereas necrotizing vasculitis was not found. Oral prednisolone therapy ameliorated the neuropathic symptoms. CONCLUSIONS AND RELEVANCE This case of IgG4-RD presented as sensory-motor neuropathy with pain and sclerosis of the skin in the extremities. The differential diagnosis of neuropathy should include IgG4-RD.
JAMA neurology. 02/2013;
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ABSTRACT: Introduction: Information related to the long-term follow-up of neuropathy in patients with familial amyloid polyneuropathy after liver transplantation is still scarce. Methods: We describe the neuropathic features of 3 patients with the transthyretin Val30Met mutation. Each patient underwent liver transplantation at an early stage of neuropathy, as indicated by the absence of motor dysfunction and relative preservation of myelinated fibers in sural nerve biopsy specimens. Results: Although the patient with late-onset disease (at age 60 years) presented with the least amount of amyloid deposition, he had neuropathic progression after liver transplantation. An older early-onset (at age 40 years) patient reported a slight exacerbation of both somatic and autonomic neuropathic symptoms 10 years after transplantation. However, the younger early-onset (at age 28 years) patient did not exhibit characteristics suggestive of neuropathy 7 years after transplantation. Conclusion: Aging may determine the progression of neuropathy after liver transplantation. Muscle Nerve, 2012.
Muscle & Nerve 12/2012; 46(6):961-4. · 2.37 Impact Factor
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ABSTRACT: Primary Sjögren's syndrome (pSS)-associated neuropathy manifests a wide variety of peripheral neuropathies that may show overlap among the neuropathic forms. In this report, we describe histopathological findings of two autopsy cases with pSS-associated neuropathy; one of them manifested the painful form and another showed ataxic form. The population of dorsal root ganglion (DRG) neurons and the density of myelinated fibers in the dorsal spinal root were variably reduced among spinal segments in both forms. In the painful form, there was a prominent reduction of small neurons, while in the ataxic form, large neurons were predominately lost. In accordance with the degree of the DRG cell loss, the modality of nerve fiber loss in the dorsal spinal roots and sural nerve correlated well with the corresponding DRG neuron loss. Prominent CD8+ T lymphocyte infiltration was present in the DRG, sympathetic ganglion, epineurial and perineurial space throughout the peripheral nerve trunks, and visceral organs, including the submandibular gland of both forms. Although the size of affected DRG neurons is different, these two forms share a similar causal mechanism, namely, cytotoxic autoimmunity to ganglion neurons, which may be one of a continuum of etiological factors. This hypothesis may have an impact on therapeutic approach.
Journal of the neurological sciences 05/2012; 319(1-2):139-46. · 2.32 Impact Factor
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ABSTRACT: To elucidate the significance of folate deficiency in alcoholic and nutritional neuropathies.
We preformed a comprehensive clinical screening of a patient with chronic alcoholism who manifested neuropathy, macrocytic anemia, liver dysfunction, and folate deficiency.
A 33-y-old woman with chronic alcoholism presented with acutely progressive glove- and stocking-type sensorimotor polyneuropathy. Although an episode of neuropathy preceded the current episode by 2 y, its cause was never determined. The findings of nerve conduction studies were indicative of axonal neuropathy. Laboratory findings revealed macrocytic anemia and liver dysfunction. Her serum level of folate was reduced, whereas thiamine, riboflavin, and cobalamin levels were within normal range. The neuropathy and anemia showed gradual recovery after the initiation of folic acid supplementation.
This case study indicates that folate deficiency should be monitored closely in patients with chronic alcoholism and associated malnutrition. Additionally, folate deficiency should be considered as a differential diagnosis of neuropathy.
Nutrition 03/2012; 28(7-8):821-4. · 3.03 Impact Factor
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Haruki Koike,
Rina Hashimoto, Minoru Tomita,
Yuichi Kawagashira,
Masahiro Iijima,
Shigeru Koyano,
Takayuki Momoo,
Hiroyuki Yuasa,
Shigehisa Mitake,
Mana Higashihara,
Kenichi Kaida,
Daisuke Yamamoto,
Shin Hisahara,
Shun Shimohama,
Yoshiharu Nakae,
Ken Johkura,
Steven Vernino,
Gen Sobue
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ABSTRACT: We assessed the clinicopathological features of nine patients with pure autonomic neuropathy, that is, neuropathy without sensory or motor deficits. The duration from symptom onset to diagnosis ranged from 1 month to 13 years. Of eight patients in whom serum antiganglionic acetylcholine receptor antibody was determined, four were positive. All patients who tested positive for this antibody manifested widespread autonomic dysfunction, with the exception of one patient who only experienced orthostatic hypotension. However, patients who were negative for the antiganglionic acetylcholine receptor antibody presented with partial autonomic failure. One of these patients had diffuse parasympathetic failure and generalized hypohidrosis but no orthostatic hypotension, which is clinically compatible with postganglionic cholinergic dysautonomia. Electron microscopic examination revealed a variable degree of reduction in unmyelinated fibers. Compared with normal controls, the patients had a significantly increased density of collagen pockets (p < 0.05). Additionally, the percentage of Schwann cell subunits with axons (out of the total number of Schwann cell subunits associated with unmyelinated fibers) was significantly decreased (p < 0.01). The density of unmyelinated fibers tended to decrease with increasing time between the onset of autonomic symptoms and biopsy (p < 0.05). In conclusion, the clinical and pathological features of pure autonomic neuropathy vary in terms of progression, autonomic involvement, presence of the antiganglionic acetylcholine receptor antibody, and loss of unmyelinated fibers.
Journal of Neurology 02/2012; 259(10):2067-75. · 3.47 Impact Factor
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Haruki Koike,
Fumiaki Tanaka,
Rina Hashimoto, Minoru Tomita,
Yuichi Kawagashira,
Masahiro Iijima,
Junko Fujitake,
Toru Kawanami,
Takeo Kato,
Masahiko Yamamoto,
Gen Sobue
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ABSTRACT: The objective of this study was to elucidate the natural history of late-onset transthyretin Val30Met-associated familial amyloid polyneuropathy (FAP ATTR Val30Met) in non-endemic areas.
The authors retrospectively assessed the development of major clinical landmarks and abnormalities of nerve conduction and cardiac examination indices in 50 patients with an age of onset older than 50 years and no relationship to endemic foci.
Once the neuropathic process was initiated, sensory and motor symptoms of both the upper and lower extremities appeared within a period of one and a half years. Digestive and orthostatic symptoms also tended to occur in the early phase of the disease, whereas urinary symptoms appeared in the middle of the disease progress. Along with pain in the extremities, these symptoms progressed over time and significantly disturbed the quality of life during the late phase of the disease, resulting in the need for wheelchair use. Although cardiomyopathy became clinically apparent only in the late phase of the disease, it was found to be the major cause of death. The mean duration of the disease onset to death was 7.3 years. Although values at the time of diagnosis were extremely variable, serial measurements of electrophysiological indices, the cardiothoracic ratio and interventricular septum thickness indicated a steady exacerbation in these outcomes among patients within a span of a couple of years.
The ages of onset of each clinical landmark were extremely variable between patients. However, once an initial symptom appeared, the chronological sequence of other clinical landmarks tended to be uniform, occurring within a relatively short time span.
Journal of neurology, neurosurgery, and psychiatry 02/2012; 83(2):152-8. · 4.87 Impact Factor
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ABSTRACT: We analyzed the 3-dimensional distribution of pathologic findings in 8 autopsied cases of neuropathy associated with microscopic polyangiitis. Necrotizing vasculitis was commonly and diffusely present in the epineurium of the sciatic/tibial and median nerves. Although findings of vasculitis were distributed diffusely in proximal to distal segments of the nerve trunks, marked loss of myelinated fibers occurred only from the middle to distal segments of these nerves. Neurons of the sensory and sympathetic ganglia were well preserved, as were myelinated fibers of the anterior and posterior spinal roots. Central fascicular nerve fiber degeneration, suggesting direct ischemic damage, occurred in restricted segments of the proximal-middle portion of the sciatic/tibial and median nerve trunks. Vasculitis was also seen in various visceral organs in all patients, but its distribution differed among individual patients; the severity of vasculitis in the other organs did not correlate with that in the peripheral nerves. The distinct spatial distribution pattern of nerve fiber degeneration, in contrast to the ubiquitous presence of vasculitis, suggested that the ischemic zone that directly damages nerve fibers is present in the proximal-middle portion of peripheral nerve trunks in microscopic polyangiitis.
Journal of Neuropathology and Experimental Neurology 05/2011; 70(5):340-8. · 4.26 Impact Factor
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ABSTRACT: Transthyretin (TTR) Val30Met-associated familial amyloid polyneuropathy (FAP ATTR Val30Met) is the most common form of FAP and is now prevalent in areas other than those seen within conventional endemic foci. We investigated 15 patients with FAP ATTR Val30Met without a family history of FAP who were referred for sural nerve biopsy. Initial symptoms included somatic neuropathy in all patients, while sensory dissociation and autonomic symptoms were apparent only in two and seven patients, respectively. Nonspecific neuropathic features and slight abnormalities in cerebrospinal fluid protein levels and in electrophysiological indices related to nerve conduction led clinicians to initially suspect chronic inflammatory demyelinating polyneuropathy (CIDP) in some patients. Small-fiber predominant loss was observed in a minority of patients. In terms of cardiac involvement, findings suggestive of subclinical cardiomyopathy due to amyloid deposition, such as cardiomegaly on chest X-ray, thickening of the interventricular septum, and granular sparkling echo on echocardiography, were seen alone or in combination in 11 of 14 examined patients. In conclusion, clinicians should consider the possibility of FAP ATTR Val30Met in patients presenting with neuropathy of undetermined etiology to avoid misdiagnosis. Detecting subclinical cardiac involvement may help to diagnose late-onset FAP ATTR Val30Met in those without a family history of the disease.
Amyloid: the international journal of experimental and clinical investigation: the official journal of the International Society of Amyloidosis 04/2011; 18(2):53-62. · 2.12 Impact Factor
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ABSTRACT: The present report describes two patients with leprous neuropathy diagnosed in Japan and manifesting with different clinical features. A 78-year-old Japanese man presented with a 3-year history of numbness and weakness affecting the upper and lower extremities. Although he did not have skin eruptions, nerve biopsy revealed acid-fast bacilli. Another patient, a 41-year-old Japanese-Brazilian man, presented with a 1-month history of numbness in the right fourth and fifth fingers and whole-body erythema. These cases highlight the fact that, as a result of worldwide travel and immigration, leprosy should still be considered in the differential diagnosis of neuropathy in developed countries.
Internal Medicine 01/2011; 50(19):2223-6. · 0.94 Impact Factor
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ABSTRACT: To characterize the morphological progression of neuropathy associated with immunoglobulin M-monoclonal gammopathy of undetermined significance with anti-myelin-associated glycoprotein antibody, we assessed histopathologic features of sural nerve specimens from 15 patients, emphasizing widely spaced myelin (WSM), demyelination, and tomaculous changes. The frequency of WSM correlated with that of demyelination and tomaculous appearance in teased-fiber preparations. In longitudinal sections at nodes of Ranvier and paranodal regions, the spaces between terminal myelin loops, particularly those adjacent to the node of Ranvier, were widened, indicating an early change before demyelination, and there was concomitant swelling of terminal myelin loops. Some conspicuously swollen terminal myelin loops were detached from the paranodal axolemma, thereby widening the nodes of Ranvier. Tomacula coexisted frequently with redundant myelin loops and WSM, particularly in the outermost layer of myelin sheaths, suggesting that loosening of the outer layers contributes to their formation. By immunofluorescence microscopy, immunoglobulin M and myelin-associated glycoprotein were colocalized in paranodal regions and Schmidt-Lanterman incisures. Confocal analysis revealed colocalization of immunoglobulin M and complement product C3d corresponding to the area of WSM. Thus, morphological changes in terminal myelin loops, formation of WSM at paranodes, and subsequent dissociation from paranodal axolemma (which may be associated with activation of the complement pathway) likely contribute to demyelination in this condition. Loosening of compact myelin seems to contribute to tomacula formation.
Journal of Neuropathology and Experimental Neurology 10/2010; 69(11):1143-57. · 4.26 Impact Factor
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Haruki Koike,
Tetsuya Kiuchi,
Masahiro Iijima,
Mitsuharu Ueda,
Yukio Ando,
Saori Morozumi, Minoru Tomita,
Yuichi Kawagashira,
Hirohisa Watanabe,
Masahisa Katsuno,
Yoshie Shimoyama,
Yasumasa Okazaki,
Hideya Kamei,
Gen Sobue
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ABSTRACT: As familial amyloid polyneuropathy (FAP) is an adult-onset disease, a long period is expected between domino liver transplantation (DLT) and the occurrence of amyloidosis in recipients of a FAP liver. However, as time passes, and increased numbers of patients have undergone DLT, patients with symptoms suggesting amyloidosis have been reported. The authors describe, for the first time, pathological findings in an autopsy case of a recipient of a FAP liver. A male patient with primary sclerosing cholangitis received a liver graft from a FAP patient with the transthyretin (TTR) Tyr114Cys mutation when he was 30 years old. Although a recurrence of primary sclerosing cholangitis was detected at age 34, he had no symptoms indicating amyloidosis. He died from Burkitt's lymphoma at 38 years of age. TTR immunoreactive amyloid was found in various organs including the heart, lung, gastrointestinal tract, pancreas, spleen, reproductive system and skeletal muscles. In the nervous system, TTR immunoreactive amyloid deposition was obvious in the sympathetic ganglia and the median nerve within the carpal tunnel, while loss of neurons or nerve fibres was not apparent. This case allows for the characterisation of amyloid deposition during the asymptomatic stage of FAP. Widespread amyloid deposition may occur before tissue damage in this disease.
Journal of neurology, neurosurgery, and psychiatry 10/2010; 82(11):1287-90. · 4.87 Impact Factor
