Lessons I have learned from my patients: everyday life with primary orthostatic tremor.

BACKGROUND: Primary orthostatic tremor is a rare disorder that is still under-diagnosed or misdiagnosed. Motor symptoms are fairly characteristics but the real impact on the patient's every day life and quality of life is under-estimated. The "how my patients taught me" format describes the impact on the patients' every day life with their own words, which is rarely done. CASE PRESENTATION: A 46 year old lady was diagnosed primary orthostatic tremor (POT) based on the cardinal symptoms: feelings of instability, leg tremor and fear of falling in the standing position, improvement with walking and disappearance while sitting, frequency of Tremor in the 13-18Hz range, normal neurological examination. She gives illustrative examples of her disability in every day life activity (shower, public transportation, shopping). She reports how she felt stigmatized by her "invisible disorder". As a consequence, she developed anxiety depression and social phobia. All these troubles are unknown or under recognized by doctors and family. CONCLUSIONS: We review the clinical signs of POT that may help to increase the awareness of doctors and improve the diagnosis accuracy, based on the motor symptoms and description of the every day life disability, as reported by the patient. Non-motor symptoms (including somatic concerns, anxiety, depression, and social phobia) should be better considered in POT as they have a major impact on quality of life. Pharmacological treatments (clonazepam, gabapentin) may be helpful but have a limited effect over the years as the patients experience a worsening of their condition. On the long term follow-up, there are still unmet needs in POT, and new therapeutic avenues may be based on the pathophysiology by modulating the cerebello-thalamo-cortical network.

Health-Related Quality of Life Is Severely Affected in Primary Orthostatic Tremor.

BACKGROUND: Primary orthostatic tremor (POT) is a movement disorder characterized by unsteadiness upon standing still due to a tremor affecting the legs. It is a gradually progressive condition with limited treatment options. Impairments in health-related quality of life (HQoL) seem to far exceed the physical disability associated with the condition. METHODS: A multi-center, mixed-methodology study was undertaken to investigate 40 consecutive patients presenting with POT to four movement disorder centers in France. HQoL was investigated using eight quantitative scales and a qualitative study which employed semi-structured interviews. Qualitative data were analyzed with a combination of grounded-theory approach. RESULTS: Our results confirm that HQoL in POT is severely affected. Fear of falling was identified as the main predictor of HQoL. The qualitative arm of our study explored our initial results in greater depth and uncovered themes not identified by the quantitative approach. CONCLUSION: Our results illustrate the huge potential of mixed methodology in identifying issues influencing HQoL in POT. Our work paves the way for enhanced patient care and improved HQoL in POT and is paradigmatic of this modern approach for investigating HQoL issues in chronic neurological disorders.

Contribution of cholesterol and oxysterols to the pathophysiology of Parkinson's disease.

Neurodegenerative diseases are a major public health issue worldwide. Some countries, including France, have engaged in research into the causes of Parkinson's disease, Alzheimer's disease, and multiple sclerosis and the management of these patients. It should lead to a better understanding of the mechanisms leading to these diseases including the possible involvement of lipids in their pathogenesis. Parkinson's disease is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra and the accumulation of α-synuclein (Lewy bodies). Several in vivo studies have shown a relationship between the lipid profile [cholesterol, oxidized cholesterol products (oxysterols) formed either enzymatically or by auto-oxidation], the use of drugs regulating cholesterol levels, and the development of Parkinson's disease. Several oxysterols are present in the brain and could play a role in the development of this disease, particularly in the accumulation of α-synuclein, and through various side effects, such as oxidation, inflammation, and cell death. Consequently, in Parkinson's disease, some oxysterols could contribute to the pathophysiology of the disease and constitute potential biomarkers or therapeutic targets.

The long-term outcome of orthostatic tremor.

OBJECTIVES: Orthostatic tremor is a rare condition characterised by high-frequency tremor that appears on standing. Although the essential clinical features of orthostatic tremor are well established, little is known about the natural progression of the disorder. We report the long-term outcome based on the largest multicentre cohort of patients with orthostatic tremor. METHODS: Clinical information of 68 patients with clinical and electrophysiological diagnosis of orthostatic tremor and a minimum follow-up of 5 years is presented. RESULTS: There was a clear female preponderance (76.5%) with a mean age of onset at 54 years. Median follow-up was 6 years (range 5-25). On diagnosis, 86.8% of patients presented with isolated orthostatic tremor and 13.2% had additional neurological features. At follow-up, seven patients who initially had isolated orthostatic tremor later developed further neurological signs. A total 79.4% of patients reported worsening of orthostatic tremor symptoms. These patients had significantly longer symptom duration than those without reported worsening (median 15.5 vs 10.5 years, respectively; p=0.005). There was no change in orthostatic tremor frequency over time. Structural imaging was largely unremarkable and dopaminergic neuroimaging (DaTSCAN) was normal in 18/19 cases. Pharmacological treatments were disappointing. Two patients were treated surgically and showed improvement. CONCLUSIONS: Orthostatic tremor is a progressive disorder with increased disability although tremor frequency is unchanged over time. In most cases, orthostatic tremor represents an isolated syndrome. Drug treatments are unsatisfactory but surgery may hold promise.