Byline: Vijay. Danivas, Nagaraj. Moily, Rohini. Thimmaiah, Kesavan. Muralidharan, Meera. Purushotham, Uday. Muthane, Sanjeev. Jain
Huntington's disease is characterized by choreic movements, psychiatric disorders, striatal atrophy with selective small neuronal loss, and autosomal dominant inheritance. The genetic abnormality is CAG expansion in Huntingtin gene. Newer therapeutic strategies are evolving to treat this progressive disorder. The neuroprotective agents are one such group of drugs being tried. Lithium has been used to treat Huntington's disease in the past due to its neuroprotective effects. Though the precise mechanism of action is not clear, Lithium can directly or indirectly modulate proteins involved in neuronal survival/differentiation which may account for its neuroprotective effects. We report three patients with Huntington's disease in whom Lithium prevented the progression of chorea and also helped stabilize mood.
Huntington's disease (HD) is an autosomal dominant, progressive neurodegenerative disorder characterized by chorea, subcortical dementia and psychiatric symptoms. The causal HD gene has been identified as IT15, which has CAG repeats in the open reading frame (ORF, in exon 1) just following the 5'end of the gene. [sup], It leads to the translation of a protein, Huntingtin, whose function is unknown. Huntingtin forms intraneuronal inclusion bodies which lead to neuronal dysfunction followed by neuronal death due to apoptosis.
The therapeutic strategies for HD are diverse, ranging from the classical drug therapies to the modern molecular strategies. One of the treatment options is the use of drugs with neuroprotective potential, like lithium. [sup], Lithium has demonstrated diverse molecular effects reversing well-described pathophysiological changes such as increased oxidative stress, apoptosis, inflammation, environmental stress, glial dysfunction, neurotrophic factor deficiency, excitotoxicity as well as mitochondrial and endoplasmic reticulum disruption. [sup], Lithium acts by inhibiting a protein- kinase called glycogen synthase kinase 3 (GSK3) that has important actions on the intracellular signal transmission by protein phosphorylation. Inhibition of this enzyme appears to have a neuroprotector effect in neurodegenerative diseases such as amyotrophic lateral sclerosis, spinocerebellar ataxia type 1 and Huntington's disease. [sup]
We report three patients with Huntington's disease, who showed good response to treatment with low dose lithium.
Mrs. A, a 48-year-old homemaker, presented in 2008 with a three-year history of involuntary movements of the trunk and the hands, which had worsened over the previous 7-8 months. She had predominantly choreic movements of both upper limbs. She also had behavioral changes such as irritability and aggression of recent onset. Family history was not available. On examination, ocular saccades were slow; she had generalized choreiform movements involving hands legs, lips and the trunk; dystonia of hands and feet and ataxic gait. MRI showed caudate atrophy. Neuropsychological assessment showed diffuse fronto-parietal and temporal involvement. A genetic analysis for Huntington's disease was performed after obtaining written informed consent which showed CAG repeat expansion. Patient was started on Lithium 150 mg, once daily, along with Carbamazepine 200 mg twice a day.
The movements have not worsened after starting Lithium and the behavioral symptoms improved completely. Patient is on regular follow up for the last four years and is maintaining the same improvement.
Mr. B, a 58-year-old male, presented in 2001 with a history of abnormal movements. These movements had started at the age of 35 years and were slowly progressive. A clinical diagnosis of Huntington's disease was made. At the time of presentation, the movements were disabling, irregular, would worsen with anxiety and disappear during sleep. …