Neurological Involvement in a Portuguese Cohort of IgG4-Related Disease.

INTRODUCTION: Neurological involvement in immunoglobulin G4-related disease (IgG4-RD) is increasingly recognized. Its diagnosis can be challenging due to clinical mimics and difficulty in obtaining nervous system biopsies. The aim of this study was to describe a cohort of neurological IgG4-RD patients. METHODS: Patients were recruited from a neuroimmunology tertiary center. Clinical, laboratory, neuroimaging and histological data were reviewed. RESULTS: Fifteen patients (60% women), with a median age of 53 years (48.5 - 65.0) were included: 13 (86.7%) classified as possible IgG4-RD, one (6.7%) as probable and one (6.7%) as definitive. The most common neurological phenotypes were meningoencephalitis (26.7%), orbital pseudotumor (13.3%), cranial neuropathies (13.3%), peripheral neuropathy (13.3%), and longitudinally extensive transverse myelitis (LTEM) (13.3%). Median serum IgG4 concentration was 191.5 (145.0 - 212.0) mg/dL. Seven in 14 patients had CSF pleocytosis (50.0%) and oligoclonal bands restricted to the intrathecal compartment, while most cases presented elevated CSF proteins (64.3%). Magnetic resonance imaging abnormalities included white matter lesions in four (26.7%), hypertrophic pachymeningitis in two (13.3%), and LETM in two (13.3%). Two patients had biopsy-proven IgG4-RD in extra-neurological sites. CONCLUSION: This study highlights the phenotypical variability of the neurological IgG4-RD. Biopsy inaccessibility reinforces the importance of new criteria for the diagnosis of this subset of patients.

Peripheral neuropathy in Parkinson's disease: prevalence and functional impact on gait and balance.

Peripheral neuropathy is a common problem in patients with Parkinson's disease. Peripheral neuropathy's prevalence in Parkinson's disease varies between 4.8-55%, compared with 9% in the general population. It remains unclear whether peripheral neuropathy leads to decreased motor performance in Parkinson's disease, resulting in impaired mobility and increased balance deficits. We aimed to determine the prevalence and type of peripheral neuropathy in Parkinson's disease patients and evaluate its functional impact on gait and balance. A cohort of consecutive Parkinson's disease patients assessed by movement disorders specialists based on the UK Brain Bank criteria underwent clinical, neurophysiological (nerve conduction studies and quantitative sensory testing) and neuropathological (intraepidermal nerve fibre density in skin biopsy punches) evaluation to characterize the peripheral neuropathy type and aetiology using a cross-sectional design. Gait and balance were characterized using wearable health-technology in OFF and ON medication states, and the main parameters were extracted using validated algorithms. A total of 99 Parkinson's disease participants with a mean age of 67.2 (±10) years and mean disease duration of 6.5 (±5) years were assessed. Based on a comprehensive clinical, neurophysiological and neuropathological evaluation, we found that 40.4% of Parkinson's disease patients presented peripheral neuropathy, with a predominance of small fibre neuropathy (70% of the group). In the OFF state, the presence of peripheral neuropathy was significantly associated with shorter stride length (P = 0.029), slower gait speed (P = 0.005) and smaller toe-off angles (P = 0.002) during straight walking; significantly slower speed (P = 0.019) and smaller toe-off angles (P = 0.007) were also observed during circular walking. In the ON state, the above effects remained, albeit moderately reduced. With regard to balance, significant differences between Parkinson's disease patients with and without peripheral neuropathy were observed in the OFF medication state during stance with closed eyes on a foam surface. In the ON states, these differences were no longer observable. We showed that peripheral neuropathy is common in Parkinson's disease and influences gait and balance parameters, as measured with mobile health-technology. Our study supports that peripheral neuropathy recognition and directed treatment should be pursued in order to improve gait in Parkinson's disease patients and minimize balance-related disability, targeting individualized medical care.

Cognitive impairment and markers of optical neurodegeneration in early multiple sclerosis.

INTRODUCTION: Cognitive impairment and retinal atrophy have been proposed as two potential markers of neurodegeneration in multiple sclerosis (MS). We aimed at assessing the relation between peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell layer (mGCL) atrophy and cognitive performance in early MS. METHODS: This is a multicenter cross-sectional study on patients with early MS (clinically isolated syndrome and relapsing-remitting MS), with an EDSS score ≤ 3.0. Patients with previous optic neuritis, other ocular diseases, psychiatric illness, or recent relapse were excluded. All patients underwent standardized optical coherence tomography (OCT) and neuropsychological evaluation with validated tests for MS patients. Cognitive impairment was defined as having two cognitive tasks below age- and education-adjusted norms. RESULTS: We recruited 52 patients with early MS, with an average age of 37 years (SD = 10.5), an average disease duration of 3.69 years (SD = 2.3), and a median EDSS of 1.0 (IQR = 0.5). In this sample, 15/52 patients presented cognitive impairment. Regarding OCT measurements, 7/52 patients had an average pRNFL below the 5th percentile and 2/52 had an average mGCL below the 5th percentile. The average pRNFL thickness was comparable in cognitively impaired and cognitively preserved patients (100.3 µm vs 103.1 µm, p = 0.52); the average mGCL thickness had also similar values between groups (50.5 µm vs 53 µm, p = 0.38). CONCLUSIONS: Cognitive impairment was frequent in our sample of early MS. However, no association with reduced pRNFL or mGCL thickness was found. When compared to OCT, cognitive assessment could provide an earlier marker of neurodegeneration in MS.

Diagnosis of Aicardi-Goutières Syndrome in Adults: A Case Series.

INTRODUCTION: Aicardi-Goutières syndrome (AGS) is a genetic disease presenting with early-onset encephalopathy, generalized dystonia, spasticity, and cognitive disability. Diagnosis may be difficult in adults, as the clinical course seems static from infancy. METHODS: AGS patients from an adult movement disorders outpatient clinic were retrospectively analyzed. RESULTS: A total of 5 patients and 1 asymptomatic carrier from 3 different families were identified. All had a homozygous c.529G>A,p.A177T mutation in exon 7 of the RNASEH2B gene. Two patients had neonatal-onset AGS, 2 had later onset forms, and 1 was slightly symptomatic. All were diagnosed in adulthood after chilblains, and basal ganglia calcifications were identified on computed tomography scans. DISCUSSION: AGS patients have marked phenotypic variability regarding psychomotor development and morbidity. The present series included 1 asymptomatic carrier and 1 slightly symptomatic patient, both with homozygous RNASEH2B mutations. Chilblains and basal ganglia calcifications identified on computed tomography scan (but not on magnetic resonance imaging) are important clues for late diagnosis.