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Polyneuropathy associated with anti-Myelin-Associated Glycoprotein (MAG) antibody is a well-defined immune-mediated disease that develops in individuals with IgM monoclonal gammopathy. Factors related to response to rituximab treatment in anti-MAG neuropathy have not been clarified so far. We prospectively evaluated the clinical status, immunological changes, and electrophysiological parameters before and 12 months after rituximab treatment in 7 patients with anti-MAG neuropathy. Pathological indices of sural nerve biopsy specimens before rituximab treatment were investigated. Overall, 4 patients improved by more than 5% either clinical scale, expressed according to the Medical Research Council (MRC) sum score or sensory sum score (SSS) 12 months after rituximab treatment. The modified Rankin Scale (mRS) scores improved in 2 patients. With respect to the relationship between the response to rituximab treatment and the clinicopathological findings, short disease duration and preservation of nerve fiber density were significantly related. The immunohistochemical assessment suggested that low-intensity binding of anti-IgM antibody to the myelin sheath may contribute to the degree of response to rituximab treatment. The degree of axonal loss and the deposition of pathogenic autoantibodies in myelinated fibers may determine the therapeutic response to rituximab treatment in anti-MAG neuropathy., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Aims: Spinocerebellar ataxia type 3 (SCA3) is an inherited spinocerebellar ataxia caused by the expansion of trinucleotide CAG repeats in the gene encoding ataxin-3. The clinical manifestations of SCA3 include peripheral neuropathy, which is an important cause of disability in a subset of patients. Although the loss of neurones in the dorsal root ganglion (DRG) has been postulated to be the cause of this neuropathy, the precise mechanism remains to be elucidated., Methods: To clarify the clinicopathological characteristics of SCA3-associated peripheral neuropathy, we performed nerve conduction studies and histopathological analyses. Nerve conduction studies were carried out in 18 SCA3 patients. Immunohistochemical analyses of the anterior and posterior roots of the spinal cord and peripheral nerves were performed in five SCA3 patients. We also employed immunohistochemistry and immunoelectron microscopy analyses with an anti-polyglutamine antibody., Results: The mean sensory nerve action potentials of the SCA3 patients were half of the normal values. The motor conduction velocities were decreased, and the distal latencies were also significantly prolonged in the nerves studied relative to the those in normal controls. Histopathological analyses detected axonal sprouting and myelin thinning in all cases. Ataxin-3 aggregates were found in the cytoplasm of Schwann cells in all of the SCA3 patients examined but not in control subjects., Conclusions: In addition to the previously reported neuronopathy, the results of the present study indicate that Schwann cells are involved in the formation of the pathogenic intracytoplasmic ataxin-3 protein aggregates in patients with SCA3-associated neuropathy., (© 2013 British Neuropathological Society.)

We describe a 54-year-old man with mononeuritis multiplex and reactive lymphoid hyperplasia with increased immunoglobulin G4 (IgG4)-positive cells. Asymmetrical numbness and weakness had advanced stepwise for 6 years. Serum immunoglobulin G, IgG4, and immunoglobulin E levels were elevated, whereas M protein was not detected. Chest and abdominal computed tomography showed generalized lymphadenopathy. Inguinal lymph node biopsy revealed expansion of the interfollicular area with infiltration of IgG4-positive cells, of which the absolute number was greater than 100 per high-power field, and the percentage of IgG4+/immunoglobulin G+ plasma cells was 33%. Sural nerve biopsy disclosed axonal neuropathy with tumefactive lymphoid infiltrate in epineurium, but IgG4-positve plasma cells and fibrosis were not detected. Symptoms and laboratory data were improved with oral glucocorticoid therapy at a dose of 0.6 mg/kg per day. Although the causal mechanisms of neuropathy should be determined in future studies, peripheral nerve involvement may occur in patients with reactive lymphoid hyperplasia with increased IgG4-positive cells., (© 2014.)

The newly recognized entity IgG4-related disease (IgG4-RD) is characterized by an elevated IgG4 serum concentration, swelling of organ, and tissue infiltration by IgG4-positive plasma cells with fibrosis. IgG4-RD has been reported in various organs. In the field of neurology, hypophysitis and hypertrophic pachymeningitis have been known to be related to IgG4-RD, while reported patients with neuropathy manifesting features compatible to IgG4-RD. The features of IgG4-related neuropathy are characterized by sensory-motor neuropathy, mononeuritis multiplex pattern, and predominant involvement of distal portions of the lower extremities. In the sural nerve biopsy specimens, fibrosis and IgG4-positive plasma cell infiltration in the epineurium and decreased myelinated fiber density due to axonal degeneration were observed. IgG4-RD should be considered as the differential diagnosis of neuropathy.

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., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Lymphoma causes various neurological manifestations that might affect any part of the nervous system and occur at any stage of the disease. The peripheral nervous system is one of the major constituents of the neurological involvement of lymphoma. In this study we characterized the clinical, electrophysiological and histopathological features of 32 patients with neuropathy associated with non-Hodgkin's lymphoma that were unrelated to complications resulting from treatment for lymphoma. Nine patients had pathologically-proven neurolymphomatosis with direct invasion of lymphoma cells into the peripheral nervous system. These patients showed lymphomatous cell invasion that was more prominent in the proximal portions of the nerve trunk and that induced demyelination without macrophage invasion and subsequent axonal degeneration in the portion distal from the demyelination site. Six other patients were also considered to have neurolymphomatosis because these patients showed positive signals along the peripheral nerve on fluorodeoxyglucose positron emission tomography imaging. Spontaneous pain can significantly disrupt daily activities, as frequently reported in patients diagnosed with neurolymphomatosis. In contrast, five patients were considered to have paraneoplastic neuropathy because primary peripheral nerve lesions were observed without the invasion of lymphomatous cells, with three patients showing features compatible with chronic inflammatory demyelinating polyneuropathy, one patient showing sensory ganglionopathy, and one patient showing vasculitic neuropathy. Of the other 12 patients, 10 presented with multiple mononeuropathies. These patients showed clinical and electrophysiological features similar to those of neurolymphomatosis rather than paraneoplastic neuropathy. Electrophysiological findings suggestive of demyelination were frequently observed, even in patients with neurolymphomatosis. Eleven of the 32 patients, including five patients with neurolymphomatosis, fulfilled the European Federation of Neurological Societies/Peripheral Nerve Society electrodiagnostic criteria of definite chronic inflammatory demyelinating polyneuropathy. Some of these patients, even those with neurolymphomatosis, responded initially to immunomodulatory treatments, including the administration of intravenous immunoglobulin and steroids. Patients with lymphoma exhibit various neuropathic patterns, but neurolymphomatosis is the major cause of neuropathy. Misdiagnoses of neurolymphomatosis as chronic inflammatory demyelinating polyneuropathy are frequent due to a presence of a demyelinating pattern and the initial response to immunomodulatory treatments. The possibility of the concomitance of lymphoma should be considered in various types of neuropathy, even if the diagnostic criteria of chronic inflammatory demyelinating polyneuropathy are met, particularly in patients complaining of pain.

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.

We herein report the case of a patient with pancreatic cancer who manifested features of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and autoimmune hemolytic anemia (AIHA). A 78-year-old Japanese man presented with AIHA and was treated with steroids and splenectomy. Although the AIHA improved following splenectomy, the patient suffered from sensorimotor neuropathy soon after undergoing surgery. The electrophysiological features indicated demyelinating neuropathy. The neuropathy was refractory to immunomodulatory treatment, and intensive investigations revealed pancreatic cancer. The patient's neurological deficits improved significantly after the surgery for cancer. Although the combination of AIHA and CIDP has been reported anecdotally, this is the first case of the coexistence of these diseases as paraneoplastic syndromes.

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., (Copyright © 2012 Wiley Periodicals, Inc.)

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.

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., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: To elucidate the significance of folate deficiency in alcoholic and nutritional neuropathies., Methods: We preformed a comprehensive clinical screening of a patient with chronic alcoholism who manifested neuropathy, macrocytic anemia, liver dysfunction, and folate deficiency., Results: 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., Conclusions: 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., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: 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., Methods: 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., Results: 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., Conclusions: 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.

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.

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.

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.

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.

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.

We report a patient with anti-myelin-associated glycoprotein (MAG) neuropathy, predominantly exhibiting severe motor symptoms, accompanied by extensive muscle atrophy mimicking Charcot-Marie-Tooth disease. Nerve conduction studies revealed mild retardation of motor conduction velocities and significant prolongation of distal latency. Sural nerve biopsy revealed widely spaced myelin and positive staining of myelinated fibers with an IgM antibody. Predominant motor symptoms with muscle atrophy can be one of the clinical manifestations of anti-MAG neuropathy.

Peripheral neuropathy associated with diabetes mellitus often causes severe neuropathic pain that is difficult to alleviate. We evaluated the effect of intravenous immunoglobulin (IVIg) therapy on six patients with two phenotypes of painful diabetic neuropathy: three patients with multifocal neuropathy and three with symmetric polyneuropathy. All patients were treated with IVIg therapy and pain levels were evaluated on the Visual Analog Scale. Three patients were also assessed by quantitative sensory testing. All three patients with multifocal neuropathy showed a marked improvement in severe pain, while the patients with symmetric polyneuropathy did not respond to IVIg therapy. Pain associated with diabetic neuropathy is multifactorial and causative factors are heterogeneous. Our results show that IVIg therapy can alleviate pain in patients with multifocal diabetic neuropathy.

Late-onset transthyretin Val30Met-associated familial amyloid polyneuropathy (FAP ATTR Val30Met) cases unrelated to endemic foci in Japan show different clinicopathological features from the conventional early-onset cases in endemic foci. We compared the characteristics of amyloid deposits in early-onset FAP ATTR Val30Met cases in endemic foci and late-onset cases in non-endemic areas. Amyloid deposits in three early-onset cases from endemic foci and five late-onset cases from non-endemic areas were systematically examined post-mortem. Amyloid deposits in early-onset cases were highly congophilic and showed strong apple-green birefringence with Congo red staining and had long, parallel fibrils in most organs. On the other hand, those in late-onset cases were generally weakly congophilic and showed faint apple-green birefringence with Congo red staining and had short, haphazard fibrils. In the renal glomus and adrenal gland of early-onset cases, the characteristics of amyloid deposits were similar to those observed in late-onset cases. Analysis of cardiac amyloid using surface enhanced desorption/ionization time-of-flight mass spectrometry indicated that most transthyretin (TTR) was variant in early-onset cases, while more than half was composed of wild-type TTR in late-onset cases. Although characteristics of amyloid deposits may differ among individual organs of respective cases, especially in early-onset cases, the pattern was distinct between early- and late-onset cases. Amyloid deposition in late-onset cases may be similar to that observed in senile systemic amyloidosis with wild-type TTR deposition, suggesting that aging may play an important role in these cases.

Background: Patients with painful sensory neuropathy associated with Sjögren's syndrome-associated neuropathy often show severe neuropathic pain which is not relieved by conventional treatments., Objective: To evaluate the effect of intravenous immunoglobulin (IVIg) therapy in the treatment of neuropathic pain associated with Sjögren's syndrome., Patients and Methods: We examined 5 patients affected by painful sensory neuropathy associated with Sjögren's syndrome. All patients were treated with IVIg (0.4 g/kg/day for 5 days) and pain rating was assessed by the Visual Analogue Scale (VAS)., Results: All five patients showed a remarkable improvement in neuropathic pain following IVIg therapy. Pain, assessed by the determination of mean VAS score, was reduced by 73.4% from days 2-14 following treatment. The observed clinical improvement persisted for 2 to 6 months. One patient, examined by quantitative sensory testing (QST), showed an improvement of superficial sensory deficit accompanied by pain relief., Conclusion: IVIg might be an effective treatment for pain in Sjögren's syndrome-associated neuropathy. Further studies should be done in a controlled, blind study.

A 57-year-old man with type 2 diabetes mellitus for 10 years showed progressive loss of muscle strength in both legs, pain and muscle atrophy in the femoral region and significant weight loss. On admission, he could not stand alone and used a wheelchair. He also complained of severe pain in the lower extremities. He was diagnosed with proximal diabetic neuropathy (PDN) by characteristic clinical and electrophysiological features. Intravenous immunoglobulin therapy (IVIg 0.4 g/kg×5 days) markedly reduced the severe pain and muscle weakness in the legs. Eventually, pain assessed by the Visual Analogue Scale was relieved by 80% and muscle strength was also well recovered, thereby enabling the patient to walk with a cane. The present case suggests that IVIg therapy may be effective for the relief of pain in PDN.

Carpal tunnel syndrome (CTS) is frequently reported in association with amyloidosis. We determined the significance of CTS in transthyretin Val30Met-associated familial amyloid polyneuropathy (FAP ATTR Val30Met) by comparing the electrophysiological indices of the median and ulnar nerves in 58 patients. As a whole, sensory nerve conduction velocity (SCV) was slowed and distal motor latency (DML) was prolonged to a similar extent in the median and ulnar nerves in these patients. The extent of abnormalities in the median nerve was almost similar to that in the ulnar nerve in both early-onset cases from endemic foci and late-onset cases from non-endemic areas. In age-matched idiopathic patients with CTS (20 patients, 27 hands), the slowing of SCV and the prolongation of DML in the median nerve were significant, while the slowing of motor conduction velocity was much less compared to FAP ATTR Val30Met patients. Although concomitant lesions in the ulnar nerve entrapment site at the wrist cannot be excluded, these findings indicate that CTS is not the sole distinctive feature in the majority of FAP ATTR Val30Met patients. The electrophysiological abnormality at the distal portion of the median nerve may be a consequence of polyneuropathy rather than an entrapment injury.