Michal Lubomski

Sex differences in Parkinson's disease.

Sex-related differences in Parkinsons disease (PD) have been recognised, but remain poorly understood. We aimed to further clarify real-life differences in disease experience according to sex, by evaluating quality of life (QoL), demographic and clinical characteristics of PD patients. A cross-sectional survey was conducted on 210 PD patients (129 men, 81 women) attending specialist neurological clinics across three centres. Outcome measures included the motor examination of the Unified Parkinsons Disease Rating Scale (UPDRS-III) and QoL as measured by the 39-item Parkinsons Disease Questionnaire (PDQ-39). A male to female ratio of 1.6:1 was observed. Men reported a greater disease burden than women as noted by higher UPDRS-III scores (27 ± 13 versus 23 ± 13, p=0.032), daily levodopa equivalent doses (898.1 ± 481.3mg versus 750.7 ± 427.2mg, p=0.037) and caregiver reliance (44% versus 29.5%, p=0.039). The UPDRS-III score was significantly associated with sex after controlling for age and disease duration, with men more severely affected (β=-0.165, r(2)=0.101, p=0.028). The PDQ-39 showed men reported lower QoL in activities of daily living (ADL), cognition and communication sub-scales (p<0.05). An association was identified in men between PDQ-39 ADL and cognition sub-scales (r=0.660, p<0.001). Men with an appointed caregiver had a higher PDQ-39 Summary Index (t=3.222, degrees of freedom=122, p=0.002). PD was found to have greater overall impact on the health and well-being of male patients in sub-specialty clinical practice. Our study further supports the need for increased sex-delineated clinical assessment and consideration of potential differences required in the management of PD.

A cross-sectional study of clinical management, and provision of health services and their utilisation, by patients with Parkinson's disease in urban and regional Victoria.

Our objective was to evaluate and compare clinical management, utilisation of health services and quality of life (QoL) in patients with Parkinsons disease (PD) attending clinics in urban and regional Victoria. A cross-sectional survey was conducted on 210 patients with PD attending specialist neurological clinics in a regional area (Ballarat) (n=97), and an urban area (Melbourne) (n=113), Victoria. Demographic characteristics of patients with PD, QoL, patterns of disease and management and utilisation of medical and allied health services were analysed. Compared to patients with PD from urban clinics, patients in the regional clinic were significantly older and were diagnosed at a later age with a shorter duration of treatment (all p<0.05). Despite no significant difference in disease severity (measured by Unified Parkinsons Disease Rating Scale scores) between the groups, patients in the urban clinic reported a lower QoL (p=0.003). Patients in the regional clinic were more satisfied with their treatment, despite seeing their medical specialist less frequently (p<0.001) and having a higher rate of early misdiagnosis (p=0.015). Patients from regional clinics reported a poorer understanding of their illness than patients in the urban clinic (p=0.049). Half of all respondents were interested in using telemedicine services. Two-thirds (71%) of all patients used allied health services, with patients in the urban clinic utilising more and desiring greater access to these services (p<0.05). In conclusion, we found significant differences in the presentation, management and use of health services between patients accessing regional and urban PD clinics in Victoria. Telemedicine may be an effective, and even desirable, method for facilitating improved diagnosis and referral for appropriate therapies.

Actinomyces cavernous sinus infection: a case and systematic literature review

A 63-year-old man presented with a 2-month history of progressive right-sided exophthalmos, painful ophthalmoplegia and fevers. As more features developed, he was diagnosed with giant cell arteritis, then Tolosa-Hunt syndrome, and transiently responded to corticosteroids. A bland cerebrospinal fluid and highly metabolically active brain (18F)-fluoro-D-glucose-positron emission tomography suggested lymphoma. Biopsy of the mass showed sulphur granules with Gram-positive filamentous bacteria with Actinomyces-like colonies. Actinomyces cavernous sinus infections are rare and indolent. They often mimic non-infective causes including other inflammatory and infiltrative conditions, vascular and neoplastic causes, particularly lymphoma. Clinicians should consider infective cavernous sinus syndromes in people with a fluctuating painful ophthalmoplegia that responds poorly to corticosteroids. The term Tolosa-Hunt syndrome is problematic and should be retired or used only with reservation.

An unusual presentation of varicella zoster virus with acute cerebellitis and SIADH without a rash

We report a case of varicella-zoster virus (VZV) infection with acute cerebellitis and encephalitis with associated Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) in an elderly man presenting with acute cerebellar ataxia without antecedent rash. Cerebrospinal fluid examination (CSF) revealed a mononuclear pleocytosis, high protein, normal glucose, positive for VZV polymerase chain reaction (PCR). Early acyclovir treatment is beneficial for acute VZV cerebellitis. Clinicians should consider infectious Central Nervous System (CNS) causes for presentations of acute cerebellar ataxia in adult patients, particularly if there is an accompanying clouded sensorium.

Rheumatoid leptomeningitis presenting with an acute neuropsychiatric disorder

Leptomeningitis is a rare central nervous system manifestation of rheumatoid arthritis, generally in patients with established chronic rheumatoid disease. We report a 41-year-old man without previous rheumatoid arthritis or psychiatric disorder who presented with an acute neuropsychiatric disturbance and polyarthralgia. His MR scan of brain showed asymmetric bifrontal leptomeningitis, confirmed on (18F)-fluoro-D-glucose-positron emission tomography. Other investigations showed highly positive serum and cerebrospinal fluid anti-cyclic citrullinated peptide. A leptomeningeal biopsy showed necrotising leptomeningeal inflammation with ill-defined granulomas and lymphoplasmacytic infiltrate without organisms. Prolonged high-dose corticosteroids and then rituximab resulted in recovery. Chronic leptomeningitis can present with an acute neuropsychiatric disorder. We highlight that early rheumatoid disease can, rarely, cause a chronic leptomeningitis, reversible with immunotherapy.

A novel Parkinson's disease risk variant, p. W378R, in the Gaucher's disease GBA gene: Parkinson's Disease and New GBA Gene Variant

Glucocerebrosidase gene (GBA) mutations cause Gaucher’s disease (GD) and confer a genetic risk factor for Parkinson’s disease (PD). Heterozygous GBA mutations may be present in 2%31% of patients with PD, suggesting they are the commonest genetic risk factors for PD. They can also be considered dominant causal genes with reduced penetrance. Lysosomal GBA enzymatic deficiency impairs α-synuclein clearance, resulting in aggregates of insoluble neuronal α-synuclein deposition. These pathogenic GBA mutations are more likely to be found in rare families manifesting both GD and PD. We describe a 3-generation family in which 8 members presented with PD and 3 with GD. The proband (IV:12) was a 66-year-oldman of English ethnicity, born to nonconsanguineous parents and diagnosed with PD with an asymmetric rest tremor, rigidity, and bradykinesia aged 56. Nine family members were available to be evaluated for GBA mutations (Fig. 1). Methods and supporting results are detailed in the Supplementary Data. Themajority of PD patients were diagnosed in their 50s with a range of 43-65 years, mean age of 54 years. They had modest to good improvementwith levodopa, but most developed early cognitive decline. The pedigree demonstrates autosomal-dominant inheritance for PD and autosomal-recessive inheritance for GD (Fig. 1). Genotypic and clinical characteristics of the kindred are presented in Table S1. The novel nucleotide change (c.1249T>C) in exon 9was confirmed by Sanger sequencing (Fig. S1) and identified in the heterozygous state in genotyped PD patients (individuals IV:12, IV:1, IV:2, IV:6, and III:9) and 3 GD patients (individuals IV:1, IV:2, and IV:3); see Figure 1. The GD siblings had compound heterozygous mutations (the common type 1 GD p.N370Smutation and the p.W378Rmutation); all had required long-term glucocerebrosidase infusions. Whole-exome sequencing of the proband excluded all other known PD gene mutations and confirmed the GBA p.W378R variant. The p.W378R GBA mutation conferred a 60% risk of developing PD across all p. W378R variant carriers, while suggesting 100% risk of developing GD for individuals who were also compound heterozygous for the p.W378R/p.N370Smutation. FIG. 1. Mean values and standard errors of (A) words per minute, (B) mean fixation duration, (C) number of regressive saccades, comparing PD in ON and OFF medication states with HCs; in (D) ANOVA of mean fixation durations of cognitively impaired (MoCA score < 26, n = 9) and cognitively normal (MoCA > 25, n = 10) PD patients and HCs. Solely cognitively impaired PD patients performed fixations with prolonged mean durations compared with HCs. (E) Fixation duration correlated with MoCA score in PD (dots, P = 0.002, R = 0.46; triangles, HCs). (F) Disease duration showed correlation with the mean regression amplitude in OFF (P = 0.0002, R = 0.57).

Encephaloclastic cyst: a rare complication of a malfunctioning methotrexate Ommaya reservoir: Letters to the Editor

at least partly with effective chemotherapy. Low-dose radiation has been shown to be an effective treatment with minimal morbidity in the setting of indolent non-Hodgkin lymphoma. In the event of failure of response of leukaemic gingivitis to chemotherapy, palliative low-dose radiation can be used for local symptom control. It is likely to be effective and well tolerated with minimal toxicity. Low-dose palliative radiation should be considered for patients with symptomatic chemotherapy resistant leukaemic deposits, such as leukaemic gingivitis.