Pharmacological Treatment of Disinhibition in Acquired Brain Injury.

PURPOSE/BACKGROUND: Traumatic brain injury is a major universal public health concern and results in chronic neurobehavioral sequelae including disinhibition. Objectives of this study were to review the literature on pharmacological treatment of disinhibition post-acquired brain injury (ABI), describe a snapshot of pharmacotherapy used in ABI at a tertiary neuropsychiatric unit in British Columbia, Canada, and share expert opinion. METHODS/PROCEDURES: A retrospective chart review of 11 patients from October to December 2021 was conducted based on exclusion criteria: age greater than 18 years, primary neurodegenerative conditions, or aphasia. Patient demographics, behavioral and cognitive test results, and disinhibition treatment were recorded. A brief review of the literature was conducted to find the best available evidence of pharmacological interventions to treat disinhibition post-ABI. FINDINGS/RESULTS: In ABI, there was a high utilization of antipsychotics and benzodiazepines, at 91% and 64% respectively, in patients with severe cognitive deficit and disinhibition. Mood stabilizers and nonselective ß-blockers were less prescribed in this population at 73% and 18%. At the point of data collection, all the patients had responded well to treatment and were in the maintenance phase of their pharmacological treatment. IMPLICATIONS/CONCLUSIONS: A limited number of studies with weak methodology suggest that mood stabilizers and ß-blockers should be first line for disinhibition treatment. Our findings are complementary to the literature describing treatment of severe disinhibition. The choice of treatment for disinhibition depends on factors including nature and severity of target symptoms, level of drug evidence, patient-tailored objectives, concurrent psychiatric diagnoses, clinical experience of clinicians, adverse drug reactions, and treatment acuity.

Action myoclonus-renal failure syndrome: characterization of a unique cerebro-renal disorder.

Action myoclonus-renal failure syndrome (AMRF) is a distinctive form of progressive myoclonus epilepsy associated with renal dysfunction. The syndrome was not recognized prior to the advent of dialysis and renal transplantation because of its rapidly fatal course if renal failure is untreated. The first and only description of AMRF was in four French Canadian patients in three families (Andermann et al., 1986). We now describe 15 individuals with AMRF from five countries, including a follow-up of the four French Canadian patients, allowing a more complete characterization of this disease. Our 15 patients with AMRF belong to nine different families. Segregation analyses were compatible with autosomal recessive inheritance. In addition, our findings show that AMRF can present with either renal or neurological features. Tremor (onset 17-26 years, mean 19.8 years, median 19 years) and progressively disabling action myoclonus (onset 14-29 years, mean 21.7 years, median 21 years), with infrequent generalized seizures (onset 20-28 years, mean 22.7 years, median 22 years) and cerebellar features are characteristic. Proteinuria, detected between ages 9 and 30 years in all cases, progressed to renal failure in 12 out of 15 patients within 0-8 years after proteinuria detection. Brain autopsy in two patients revealed extraneuronal pigment accumulation. Renal biopsies showed collapsing glomerulopathy, a severe variant of focal glomerulosclerosis. This study extends the AMRF phenotype, and demonstrates a more extensive ethnic and geographic distribution of a syndrome originally believed to be confined to individuals of French Canadian ancestry. The independent progression of neurological and renal disorders in AMRF suggests a unitary molecular lesion with pleiotropic effects. Our results demonstrate that the renal lesion in AMRF is a recessive form of collapsing glomerulopathy. Genes identified for focal segmental glomerulosclerosis and involved with the function of the glomerular basement membrane and related proteins are thus good candidates. Treatment can improve quality of life and extend the lifespan of these patients. Dialysis and renal transplantation are effective for the renal but not the neurological features, which continue to progress even in the presence of normalized renal function; the latter can be managed with anti-myoclonic and anti-epileptic drugs.