Untreated Classic Galactosemia: A Rare Cause of Adult-Onset Progressive Cerebellar Ataxia - A Case Report.

Introduction: Identifying the underlying etiology of nonfamilial adult-onset progressive cerebellar ataxia is often challenging because neurologists must consider almost all nongenetic and genetic causes of ataxia. Case Presentation: A 39-year-old woman was hospitalized for progressive ataxia with pyramidal and cognitive dysfunction after a right arm shaking and coordination problem deteriorated progressively over 1.5 years. The patient's medical history included amenorrhea, cataracts, developmental delays, consanguinity of the parents, motor coordination issues, and diarrhea and vomiting in infancy. An important finding that enabled us to solve the diagnostic conundrum was the elevated carbohydrate-deficient transferrin levels in the lack of alcohol-related symptoms, which also occur in untreated carbohydrate metabolism disorders, sometimes with ataxia as a leading symptom. The decreased erythrocyte galactose-1-phosphate uridyltransferase (GALT) enzyme activity and the elevated erythrocyte galactose-1-phosphate (Gal-1P) concentration led to the final diagnosis of galactosemia, a rare metabolic disorder. The patient's condition stayed stable with strict adherence to lactose-free and galactose-restricted diets, regular physiotherapy, and speech therapy, despite attempts to control the crippling tremor. Conclusion: This case highlights the importance of considering rare diseases based on unexplained clinical and laboratory findings. Newborn screening does not change the long-term complications of early-treated classical galactosemia. A small percentage of these patients develop ataxia tremor syndrome.

Deep Brain Stimulation: When to Test Directional?

Background: Directional deep brain stimulation (DBS) allows for steering of the stimulation field, but extensive and time-consuming testing of all segmented contacts is necessary to identify the possible benefit of steering. It is therefore important to determine under which circumstances directional current steering is advantageous. Methods: Fifty two Parkinson's disease patients implanted in the STN with a directional DBS system underwent a standardized monopolar programming session 5 to 9 months after implantation. Individual contacts were tested for a potential advantage of directional stimulation. Results were used to build a prediction model for the selection of ring levels that would benefit from directional stimulation. Results: On average, there was no significant difference in therapeutic window between ring-level contact and best directional contact. However, according to our standardized protocol, 35% of the contacts and 66% of patients had a larger therapeutic window under directional stimulation compared to ring-mode. The segmented contacts warranting directional current steering could be predicted with a sensitivity of 79% and a specificity of 57%. Conclusion: To reduce time required for DBS programming, we recommend additional directional contact testing initially only on ring-level contacts with a therapeutic window of less than 2.0 mA.

Reckless Generosity, Parkinson's Disease and Dopamine: A Case Series and Literature Review.

BACKGROUND: Impulse control disorders (ICDs) are a frequent side effect of dopamine replacement therapy (DRT) in Parkinson's disease (PD). Reckless generosity might expand the spectrum of known ICDs. CASES: Over 18 months, we encountered three PD patients exhibiting reckless generosity under DRT, leading to disastrous financial and social consequences. LITERATURE REVIEW: Except for another case series describing reckless generosity in three PD patients, only one study has examined generosity in PD patients; with findings suggesting that PD patients with ICDs are less sensitive to the aversive aspects of the lack of reciprocation in social settings. Studies with healthy individuals suggest that increased availability of dopamine might reduce social discounting and promote egalitarian behavior, and thereby increase generous behavior towards strangers. Genetic studies show that polymorphisms in dopamine D4 receptors influence generous behavior. CONCLUSIONS: Reckless generosity in PD patients with DRT might be underreported and should therefore be carefully be screened for by clinicians. A potential mechanism underlying this ICD-related behavior might be a sensitization of the mesolimbic and mesocortical dopaminergic system, leading to reduced social discounting and maladaptive reward-learning. Further research is needed to investigate the prevalence and underlying mechanisms of reckless generosity in PD patients.

Depression in blepharospasm: a question of facial feedback?

Depression is the most important nonmotor symptom in blepharospasm (BL). As facial expression influences emotional perception, summarized as the facial feedback hypothesis, we investigated if patients report fewer depressive symptoms if injections of botulinum neurotoxin (BoNT) include the "grief muscles" of the glabellar region, compared to treatment of orbicularis oculi muscles alone. Ninety BL patients were included, half of whom had BoNT treatment including the frown lines. While treatment pattern did not predict depressive symptoms overall, subgroup analysis revealed that in male BL patients, BoNT injections into the frown lines were associated with remarkably less depressive symptoms. We hypothesize that in BL patients presenting with dystonia of the eyebrow region, BoNT therapy should include frown line application whenever justified, to optimize nonmotor effects of BoNT denervation.