PracticeUpdate: Neurology - Winter 2018

EDITOR’S PICKS 10

Functional Neurological Disorders in Parkinson’s Disease Journal of Neurology, Neurosurgery, and Psychiatry Take-home message • Functional neurologic disorders (FNDs) are common and underrecog- nized. They frequently occur together with a different, organic disorder, posing diagnostic and therapeutic challenges. This is a multicenter case–control study in several countries, assessing the clinical and demographic features of FNDs in patients with Parkinson’s disease (PD). Functional symptoms preceded PD onset or occurred at the same time in 34% of cases and were typically seen on themost affected side. Patients with coexisting FNDs had longer delay to PD diagnosis and received a DAT scan to assist diagnosis more frequently. Psychiatric disorders and family history of PD were more common when FNDs were associated. PD-FND patients had higher mean scores on the Beck Depression Inventory (34 vs 17) and the Beck Anxiety Inventory (21 vs 14). Healthcare utilization was higher, including more hospitaliza- tions (mean, 1.2 vs 0.9). The most common functional symptoms were gait/balance dysfunction and tremor. • This article draws attention to the prevalence of FNDs in PD and offers useful information on clinical details. Codrin Lungu MD Abstract

Encephalitis WithmGluR5 Antibodies Neurology

Take-home message • This case series outlines the features and evo- lution of metabotropic glutamate receptor 5 (mGluR5) antibody-associated encephalitis. Clin- ically, the condition is associated with a complex neuropsychiatric syndrome, with psychiatric and cognitive features present in most patients. Sev- eral patients had prodromal features consisting most often of weight loss or headache. Of the 11 patients, 6 had an associated cancer, most commonly Hodgkin’s lymphoma. Response to immunotherapy appears to be typical (with ster- oids often the first-line treatment), but relapse was seen, both with and without an associated tumor. • This report is a useful reference for this rare condition. Codrin Lungu MD Abstract OBJECTIVE To report the clinical features of 11 patients with metabotropic glutamate receptor 5 (mGluR5) antibody-associ- ated encephalitis, immunoglobulin G (IgG) subclass, and effects of the antibodies on neuronal mGluR5 clusters. METHODS Clinical information was retrospectively obtained from referring physicians. Antibodies to mGluR5 and IgG subclasses were determined with brain immunohistochemistry and cell- based assays. The effects of the antibodies were examined on rat hippocampal neurons with reported techniques. RESULTS From January 2005 to May 2017, 11 patients (median age 29 years, range 6-75 years, 5 female) were identified. The main clinical features were psychiatric (10), cognitive (10), movement disorders (7), sleep dysfunction (7), and seizures (6). Median modified Rankin Scale score at the peak of the dis- ease was 4; 4 patients required intensive care. Five patients had Hodgkin lymphoma, and 1 had small cell lung cancer. CSF showed pleocytosis (median white blood cell count 22 mm3) in all patients; brain MRI was abnormal in 5, involving limbic (1) or extralimbic (4) regions. Treatments included immunother- apy and/or oncologic therapy; at the last follow-up (median 48 months), 6 patients had complete and 5 had partial recovery. Neurologic relapse occurred in 2 patients. Antibodies were IgG1 alone (4 of 9) or in combination with IgG2 (1 of 9), IgG3 (3 of 9), or both (1). Patients’ IgG caused a significant and specific decrease of cell-surface synaptic and extrasynaptic mGluR5 without altering the levels of postsynaptic density protein 95. CONCLUSIONS Anti-mGluR5 encephalitis associates with a complex neuropsychiatric syndrome, not restricted to limbic encephalitis, and can occur without tumor. Patients respond to treatment, but relapses can occur. The antibodies have pathogenic effects altering the levels of cell-surface mGluR5. Encephalitis With mGluR5 Antibodies: Symptoms and Anti- body Effects. Neurology 2018 May 29;90(22)e1964-e1972, M Spatola, L Sabater, J Planagumà, et al. www.practiceupdate.com/c/68853

OBJECTIVE To ascertain demographic and clinical features of Parkinson dis- ease (PD) associated with functional neurological features. METHODS A standardised form was used to extract data from electronic records of 53 PD patients with associated func- tional neurological disorders (PD-FND) across eight movement disorders cen- tres in the USA, Canada and Europe. These subjects were matched for age, gender and disease duration to PD patients without functional features (PD-only). Logistic regression analysis was used to compare both groups after adjusting for clustering effect. RESULTS Functional symptoms preceded or co-occurred with PD onset in 34% of cases, nearly always in the most affected body side. Compared with PD-only subjects, PD-FND were pre- dominantly female (68%), had longer delay to PD diagnosis, greater prev- alence of dyskinesia (42% vs 18%; P=0.023), worse depression and anxi- ety (P=0.033 and 0.025, respectively), higher levodopa-equivalent daily dose (972±701 vs 741±559mg; P=0.029) and lower motor severity (P=0.019). These patients also exhibited greater health- care resource utilisation, higher use of [(123)I]FP-CIT SPECT and were more likely to have had a pre-existing psy- chiatric disorder (P=0.008) and family history of PD (P=0.036).

CONCLUSIONS A subtype of PD with func- tional neurological features is familial in one-fourth of cases and associated with more psychiatric than motor dis- ability and greater use of diagnostic and healthcare resources than those without functional features. Functional manifestations may be prodromal to PD in one-third of patients. Functional Neurological Disorders in Parkinson Disease. J Neurol Neurosurg Psychiatr 2018 Jun 01;89(6)566-571, BD Wissel, AK Dwivedi, A Merola, et al. www.practiceupdate.com/c/68819

PRACTICEUPDATE NEUROLOGY