Subclinical peripheral neuropathy is common in neuronal intranuclear inclusion disease with dominant encephalopathy

Abstract

Background and purpose: Neuronal intranuclear inclusion disease (NIID) is associated with CGG repeat expansion in the NOTCH2NLC gene. Although pure or dominant peripheral neuropathy has been described as a subtype of NIID in a few patients, most NIID patients predominantly show involvements of the central nervous system (CNS). It is necessary to further explore whether these patients have subclinical peripheral neuropathy.Methods: Twenty-eight NIID patients, clinically characterized by CNS-dominant involvements, were recruited from two tertiary hospitals. Standard nerve conduction studies were performed in all patients. Skin and sural nerve biopsies were performed in 28 and 15 patients, respectively. Repeat-primed polymerase chain reaction and amplicon length polymerase chain reaction were used to screen the CGG repeat expansion in NOTCH2NLC.Results: All 28 patients can be diagnosed with NIID based on skin pathological and genetic changes. All patients predominantly showed CNS symptoms mainly characterized

NOTCH2NLC‐related oculopharyngodistal myopathy type 3 with cardiomyopathy and nephropathy

“…3 Patients with NIID usually present with heterogeneous clinical symptoms, including leukoencephalopathy, dementia, ataxia, and autonomic dysfunction. 4 Subclinical peripheral neuropathy is also common and primary demyelinating impairment accompanied by mild axonal degeneration is the main pattern. 4 The patient here presented with leukoencephalopathy and dysautonomia in addition to weakness in ocular, facial, pharyngeal, and distal limb muscles, which was indicative of the overlapping phenotypes of NIID and OPDM3.…”

A case report of neuronal intranuclear inclusion disease with paroxysmal peripheral neuropathy-like onset lacking typical signs on diffusion-weighted imaging

“…Overall, predominate demyelinating with mild axonal impairments are the primary electrophysiological pattern of NIID. The demyelinating impairments are homogeneous, extensive, and slight which presented with comprehensively decreased nerve conduction velocity and prolonged latency of F-waves and H-reflexes (13). This unique electrophysiological pattern provides subtle clues for differential diagnosis of NIID with other peripheral neuropathies from the functional perspective (14).…”

Skin biopsy and neuronal intranuclear inclusion disease

“…According to the initial presentation and main symptoms in two recent cohorts, the clinical classification of NIID could be divided into five distinct types: cognitive impairment dominant, movement disorder dominant, episodic neurogenic symptom dominant, autonomic dysfunction dominant, and neuromuscular disorder dominant 20,21 . In addition, progressive retinal degeneration, primary intestinal pseudo‐obstruction, unexplained dry cough, and idiopathic urinary incontinence or retention may precede the neurological manifestations and provide a clinical basis for the early intervention and staging of the disease, although no effective treatment is currently available for NIID 22,23 …”

“…20,21 In addition, progressive retinal degeneration, primary intestinal pseudo-obstruction, unexplained dry cough, and idiopathic urinary incontinence or retention may precede the neurological manifestations and provide a clinical basis for the early intervention and staging of the disease, although no effective treatment is currently available for NIID. 22,23 High-intensity signals along the corticomedullary junction on diffusion-weighted imaging (DWI) were observed in most patients with adult-onset NIID and considered as a valuable marker for the diagnosis of NIID (Figure 1a). 24 However, the patients with NIID presenting with specific phenotypes or at the early stage might be misdiagnosed because of atypical radiological features or absence of DWI abnormalities.…”