Alexander Lehn

Functional neurological disorders: mechanisms and treatment.

Functional neurological disorders are common problems in neurologic practice. In the past decade there has been an increasing interest in this group of disorders both from a clinical as well as research point of view. In this review, we highlight some of the most salient and exciting publications from recent years focusing especially on new findings illuminating mechanism and studies examining treatment.

Psychiatric disorders in idiopathic-isolated focal dystonia

Abstract Idiopathic-isolated focal dystonia (IIFD) is a movement disorder characterised by involuntary, sustained muscle contractions, leading to abnormal postures. Psychopathology is frequent in patients with IIFD, and while traditionally this was thought to be a secondary phenomenon, there is emerging evidence for shared neurobiological mechanisms. We conducted a single-centre cross-sectional study of 103 consecutive patients with IIFD and two comparison groups: 78 consecutive patients with hemifacial spasm (HFS) and 93 healthy control subjects. Assessments with regard to psychiatric disturbances were performed using self-report questionnaires, including the self-report version of the Yale–Brown Obsessive Compulsive Scale (Y-BOCS-SR), the Beck Anxiety Inventory (BAI), and the Beck Depression Inventory (BDI). Compared to healthy control subjects and patients with HFS, the IIFD group had higher OCS, anxiety, and depression scores as measured by the Y-BOCS-SR, BAI, and BDI, respectively. The Y-BOCS-SR, BAI, and BDI were highly correlated across all the subjects. Logistic regression analysis showed that the main driver of high obsessive–compulsive symptom scores, irrespective of neurological diagnosis, was the BDI, whereas it was BAI (and not BDI), that drives the association between the psychiatric rating scale scores and the neurological diagnosis. Our findings suggest that while clinically significant obsessive–compulsive symptoms are over-represented in IIFD patients relative to controls, the BAI may have better discriminatory power to distinguish between the psychiatric symptoms in IIFD patients.

Dopamine dysregulation syndrome in Parkinson’s disease: a systematic review of published cases

Objectives Dopamine dysregulation syndrome (DDS) is an uncommon complication of the treatment of Parkinson’s disease, characterised by addictive behaviour and excessive use of dopaminergic medication. DDS may frequently go unrecognised or misdiagnosed. We aimed to clarify current understanding of presentation, risk factors, comorbidities and management of DDS. Methods Case reports were identified through a systematic search of databases (PubMed, Embase) with the following terms: dopaminergic dysregulation syndrome, hedonistic homeostatic dysregulation, dopamine/levodopa addiction. Results We reviewed 390 articles, identifying 98 cases of DDS. Early-onset Parkinson’s disease (67%) and male gender (83%) were common. DDS presented with significant physical and social impairment, actions to enable or prevent detection of overuse, as well as mood, anxiety and motor fluctuations. All DDS cases met DSM-V (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) substance use disorder criteria. Past substance and psychiatric history was present in 15.3% and 10.2% of cases. Comorbid impulse control disorders (61%), psychosis (32%) and panic attacks (14%) were common. A large variety of management strategies were used; only 56% of cases resolving. Sodium valproate was successful in 5/5 cases. The response to deep brain stimulation varied. Conclusions Given the functional impairment, medical and psychiatric consequences and the difficulties of treatment, early identification of DDS should be a priority.

Chapter 5 - Epidemiology

The epidemiology of functional neurologic disorders (FND) is complex and has been hampered over the years by a lack of clear definition, with previous definitions struggling with an uneasy mix of both physical and psychologic components. The recent changes in DSM-5 to a definition based on positive identification of physical symptoms which are incongruent and inconsistent with neurologic disease and the lack of need for any associated psychopathology represent a significant step forward in clarifying the disorder. On this basis, FND account for approximately 6% of neurology outpatient contacts and putative community incidence rates of 4–12 per 100 000 per annum. Comorbid neurologic disease occurs in around 10% of cases. The diagnosis is reliable, with revision rates less than 5%. Of note, this revision rate was consistent prior to the widespread utilization of computed tomography and magnetic resonance imaging. FND symptoms are disabling and associated with significant distress. They are more common in women and have a peak incidence between the ages of 35 and 50; however the presentation is common in men and throughout the lifespan. The issues surrounding case definition, ascertainment, misdiagnosis, and risk factors are discussed in detail.

Screening for rare sequence variants in the THAP1 gene in a primary dystonia cohort.

The screening of primary dystonia cases has identified >50 potential disease-causing sequence variants in THAP1, the causative gene for DYT6 dystonia. One-third of these mutations occur in patients with adult-onset forms of dystonia. We report on the identification of a novel variant following a comprehensive examination of the THAP1 gene in a series of adult-onset primary dystonia patients from Queensland, Australia.

A case of bilateral lower cranial nerve palsies after base of skull trauma With complex management issues case report and review of the literature

Introduction: Fractures of the skull base can cause lower cranial nerve palsies because of involvement of the nerves as they traverse the skull. A variety of syndromes have been described, often involving multiple nerves. These are most commonly unilateral, and only a handful of cases of bilateral cranial nerve involvement have been reported. Case Report: We describe a 64-year-old man with occipital condylar fracture complicated by bilateral palsies of IX and X nerves associated with dramatic physiological derangement causing severe management challenges. Apart from debilitating postural hypotension, he developed dysphagia, severe gastrointestinal dysmotility, issues with airway protection as well as airway obstruction, increased oropharyngeal secretions and variable respiratory control. Conclusions: This is the first report of a patient with traumatic bilateral cranial nerve IX and X nerve palsies. This detailed report and the summary of all 6 previous case reports of traumatic bilateral lower cranial nerve palsies illustrate clinical features, treatment strategies, and outcomes of these rare events.

iPad colour vision apps for dyschromatopsia screening

Optic neuritis (ON) is a common and important cause of vision loss or vision disturbances in the community, particularly amongst the young, and it is often associated with a persistent dyschromatopsia. Traditionally screening for dyschromatopsia has been carried out using pseudo-isochromatic Ishihara plates. These colour plates were originally developed for testing of colour blindness, and indeed have only more recently been applied to ON. As the Ishihara plate books used for testing are expensive, unwieldy, and are not commonly available in many clinics or wards, many neurologists and ophthalmologists have taken to using untested and unstudied downloadable software packages on portable electronic devices for testing. This study compared the efficacy of printed and iPad (Apple, Cupertino, CA, USA) versions of the Ishihara plates in screening for dyschromatopsia in patients who were suspected of having ON. The main finding was that dyschromatopsia testing using a commercially available application on an iPad was comparable to using the current pragmatic clinical benchmark, the pseudo-isochromatic plates of Ishihara. These findings provide support for the increasingly common practice of screening for dyschromatopsia using the iPad.

Immunoglobulin-responsive refractory epilepsy – 3 cases with a similar EEG pattern

Autoimmune epilepsies are a heterogeneous group of recently described refractory epilepsies. They have been characterized by a variety of clinical, serological and radiological features. A range of anti-neuronal antibodies, which are usually found in limbic encephalitis, including antibodies to GAD, VGKC-complex antibodies, NMDA-R, amongst others, have been associated with some of these disorders. Other, antibody negative epilepsy patients had radiological features of central nervous system inflammation, inflammatory infiltrates histologically or high CSF white cell counts and oligoclonal bands. Immune therapy, including steroids and IVIg, has been used in these cases and resulted in clinical improvement. Best outcomes were associated with a short duration of the underlying illness. Long-term immune therapy has often been utilized in these cases. In this article, we describe a small cohort of patients who had a rapid, sustained response to a short course of IVIg, despite limited

Olfactory impairment and pathology in neurodegenerative disorders with brain iron accumulation.

Olfaction was tested using the 40-item smell identification test (UPSIT; for references see supplementary material online) in an appropriate cultural format for each patient (http://www.sensonics.com). Cognitive function was scored by mini-mental state examination. NBIA patients were enrolled if they were non-demented (MMSE > 24), able to speak and had no nasal pathology. UPSIT scores were compared between controls and patients with NBIA using a multivariate model adjusting for cognition. Post-mortem olfactory bulb tissue from a 56-year-old man with aceruloplasminemia was examined for iron (Perl’s stain; see supplementary material). Olfactory bulb, tract and cortex from 2 pathologically diagnosed NBIA cases (2 female, aged 77 and 65) and Neurodegenerative disorders with brain iron accumulation (NBIA) are a clinically and genetically heterogeneous group of neurodegenerative diseases featuring excessive brain iron deposition [2]. Iron deficient mice display impaired olfactory behaviour and chronic exposure to airborne iron particles is associated with hyposmia [4]. We hypothesised that dysregulated brain iron metabolism in NBIA might be associated with hyposmia. We tested olfactory function in a group of NBIA patients and performed histological examination of olfactory tissue from patients with NBIA and a mouse NBIA model for iron deposition.

Teaching NeuroImages: Neuroferritinopathy

A 51-year-old music teacher presented with difficulty playing his flute and mild dysarthria related to impaired tongue movements. Over the subsequent 11 years, he developed fluctuating chorea and bradykinesis, stereotypic foot tapping, and a grossly unsteady gait, …