We assessed the clinicopathological features of 92 patients with primary Sjögren's syndrome-associated neuropathy (76 women, 16 men, 54.7 years, age at onset). The majority of patients (93%) were diagnosed with Sjögren's syndrome after neuropathic symptoms appeared. We classified these patients into seven forms of neuropathy: sensory ataxic neuropathy (n = 36), painful sensory neuropathy without sensory ataxia (n = 18), multiple mononeuropathy (n = 11), multiple cranial neuropathy (n = 5), trigeminal neuropathy (n = 15), autonomic neuropathy (n = 3) and radiculoneuropathy (n = 4), based on the predominant neuropathic symptoms. Acute or subacute onset was seen more frequently in multiple mononeuropathy and multiple cranial neuropathy, whereas chronic progression was predominant in other forms of neuropathy. Sensory symptoms without substantial motor involvement were seen predominantly in sensory ataxic, painful sensory, trigeminal and autonomic neuropathy, although the affected sensory modalities and distribution pattern varied. In contrast, motor weakness and muscle atrophy were observed in multiple mononeuropathy, multiple cranial neuropathy and radiculoneuropathy. Autonomic symptoms were often seen in all forms of neuropathy. Abnormal pupils and orthostatic hypotension were particularly frequent in sensory ataxic, painful, trigeminal and autonomic neuropathy. Unelicited somatosensory evoked potentials and spinal cord posterior column abnormalities in MRI were observed in sensory ataxic, painful and autonomic neuropathy. Sural nerve biopsy specimens (n = 55) revealed variable degrees of axon loss. Predominantly large fibre loss was observed in sensory ataxic neuropathy, whereas predominantly small fibre loss occurred in painful sensory neuropathy. Angiitis and perivascular cell invasion were seen most frequently in multiple mononeuropathy, followed by sensory ataxic neuropathy. The autopsy findings of one patient with sensory ataxic neuropathy showed severe large sensory neuron loss paralleling to dorsal root and posterior column involvement of the spinal cord, and severe sympathetic neuron loss. Degrees of neuron loss in the dorsal and sympathetic ganglion corresponded to segmental distribution of sensory and sweating impairment. Multifocal T-cell invasion was seen in the dorsal root and sympathetic ganglion, perineurial space and vessel walls in the nerve trunks. Differential therapeutic responses for corticosteroids and IVIg were seen among the neuropathic forms. These clinicopathological observations suggest that sensory ataxic, painful and perhaps trigeminal neuropathy are related to ganglioneuronopathic process, whereas multiple mononeuropathy and multiple cranial neuropathy would be more closely associated with vasculitic process.

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The pathology of early- and late-onset FAP TTR Met30 correlated well with differences in clinical findings.

Characteristics of alcoholic neuropathy have been obscured by difficulty in isolating them from features of thiamine-deficiency neuropathy. We assessed 64 patients with alcoholic neuropathy including subgroups without (ALN) and with (ALN-TD) coexisting thiamine deficiency. Thirty-two patients with nonalcoholic thiamine-deficiency neuropathy (TDN) also were investigated for comparison. In ALN, clinical symptoms were sensory-dominant and slowly progressive, predominantly impairing superficial sensation (especially nociception) with pain or painful burning sensation. In TDN, most cases manifested a motor-dominant and acutely progressive pattern, with impairment of both superficial and deep sensation. Small-fiber-predominant axonal loss in sural nerve specimens was characteristic of ALN, especially with a short history of neuropathy; long history was associated with regenerating small fibers. Large-fiber-predominant axonal loss predominated in TDN. Subperineurial edema was more prominent in TDN, whereas segmental de/remyelination resulting from widening of consecutive nodes of Ranvier was more frequent in ALN. Myelin irregularity was greater in ALN. ALN-TD showed a variable mixture of these features in ALN and TDN. We concluded that pure-form of alcoholic neuropathy (ALN) was distinct from pure-form of thiamine-deficiency neuropathy (TDN), supporting the view that alcoholic neuropathy can be caused by direct toxic effect of ethanol or its metabolites. However, features of alcoholic neuropathy is influenced by concomitant thiamine-deficiency state, having so far caused the obscure clinicopathological entity of alcoholic neuropathy.

ObjectiveTo investigate the morphological features of chronic inflammatory demyelinating polyneuropathy (CIDP) with autoantibodies directed against paranodal junctional molecules, particularly focusing on the fine structures of the paranodes.MethodsWe assessed sural nerve biopsy specimens obtained from 9 patients with CIDP with anti-neurofascin-155 antibodies and 1 patient with anti-contactin-1 antibodies. 13 patients with CIDP without these antibodies were also examined to compare pathological findings.ResultsCharacteristic light and electron microscopy findings in transverse sections from patients with anti-neurofascin-155 and anti-contactin-1 antibodies indicated a slight reduction in myelinated fibre density, with scattered myelin ovoids, and the absence of macrophage-mediated demyelination or onion bulbs. Teased-fibre preparations revealed that segmental demyelination tended to be found in patients with relatively higher frequencies of axonal degeneration and was tandemly found at consecutive nodes of Ranvier in a single fibre. Assessment of longitudinal sections by electron microscopy revealed that detachment of terminal myelin loops from the axolemma was frequently found at the paranode in patients with anti-neurofascin-155 and anti-contactin-1 antibody-positive CIDP compared with patients with antibody-negative CIDP. Patients with anti-neurofascin-155 antibodies showed a positive correlation between the frequencies of axo–glial detachment at the paranode and axonal degeneration, as assessed by teased-fibre preparations (p<0.05).ConclusionsParanodal dissection without classical macrophage-mediated demyelination is the characteristic feature of patients with CIDP with autoantibodies to paranodal axo–glial junctional molecules.