Response of Motor Complications in Cockayne Syndrome to Carbidopa-Levodopa

Abstract

Background: Gait difficulties, tremors, and coordination difficulties are common features of Cockayne syndrome that are consequences of leukodystrophy, cerebellar atrophy, and demyelinating neuropathy, but no pharmacotherapy for these disabling symptoms is available. Objective: To determine whether carbidopa-levodopa relieves tremors and other motor complications of Cockayne syndrome. Design: Mutation analysis and case report study. Setting: Hospital clinic and genetics research laboratory. Patients: We studied 3 patients with Cockayne syndrome, a rare autosomal recessive neurodegenerative disorder for which no known treatments are available. Intervention: Carbidopa-levodopa therapy. Main Outcome Measures: Status of tremors, ability to perform daily tasks, serial physical examinations, and results of handwriting samples. Results: All 3 patients had a clear reduction in tremors and improvements in handwriting and manipulation of utensils and cups. Conclusions: Patients with Cockayne syndrome should be evaluated carefully for movement disorders. A clinical trial should be considered to evaluate this therapy further.

Cognitive Decline and Other Late-Stage Neurologic Complications in Cockayne Syndrome

“…While these symptoms are not specific to dementia, our participants' accelerated brain atrophy along with informant reported decline in cognition and behavior are core features of the NIA-AA criteria for all-cause dementia. 19 While tremors and neuropathy were found in the majority of our participants, with onset at younger ages consistent with previous reports, 1,15 neurocognitive/neuropsychiatric decline, strokes, and seizures tended to occur later in the disease course. Pathogenic variants in ERCC6 have generally been considered to be associated with more severe CS phenotypes.…”

Cognitive Decline and Other Late-Stage Neurologic Complications in Cockayne Syndrome

“…While these symptoms are not specific to dementia, our participants' accelerated brain atrophy along with informant reported decline in cognition and behavior are core features of the NIA-AA criteria for all-cause dementia. 19 While tremors and neuropathy were found in the majority of our participants, with onset at younger ages consistent with previous reports, 1,15 neurocognitive/neuropsychiatric decline, strokes, and seizures tended to occur later in the disease course. Pathogenic variants in ERCC6 have generally been considered to be associated with more severe CS phenotypes.…”

A Case of ERCC6‐Related Cockayne Syndrome Presenting with Levodopa‐Responsive Tremor Syndrome

“…No definitive treatment has been introduced for CS. 8 A presentation of tremor and dysmetria responsive to treatments such as carbidopa-levodopa was reported in previous literature, 9 and our patient responded to botulinum toxin as well.…”

Nationwide survey of Cockayne syndrome in Japan: Incidence, clinical course and prognosis

“…reported that 9/21 adult patients had movement disorders (resting tremors in six cases and choreoathetosis in three cases) . Deep brain stimulation or oral carbidopa–levodopa was reported to be clinically effective in some CS patients with movement disorders (dystonia) . We also noted improvement of hand tremor in CS type 3 patients after addition of an oral synthetic thyrotropin‐releasing hormone analog, which has been widely used for treatment of spinocerebellar degeneration.…”

Cognitive Decline and Other Late-Stage Neurologic Complications in Cockayne Syndrome

“…While these symptoms are not specific to dementia, our participants' accelerated brain atrophy along with informant reported decline in cognition and behavior are core features of the NIA-AA criteria for all-cause dementia. 19 While tremors and neuropathy were found in the majority of our participants, with onset at younger ages consistent with previous reports, 1,15 neurocognitive/neuropsychiatric decline, strokes, and seizures tended to occur later in the disease course. Pathogenic variants in ERCC6 have generally been considered to be associated with more severe CS phenotypes.…”

A Case of ERCC6‐Related Cockayne Syndrome Presenting with Levodopa‐Responsive Tremor Syndrome

“…No definitive treatment has been introduced for CS. 8 A presentation of tremor and dysmetria responsive to treatments such as carbidopa-levodopa was reported in previous literature, 9 and our patient responded to botulinum toxin as well.…”

Nationwide survey of Cockayne syndrome in Japan: Incidence, clinical course and prognosis

“…reported that 9/21 adult patients had movement disorders (resting tremors in six cases and choreoathetosis in three cases) . Deep brain stimulation or oral carbidopa–levodopa was reported to be clinically effective in some CS patients with movement disorders (dystonia) . We also noted improvement of hand tremor in CS type 3 patients after addition of an oral synthetic thyrotropin‐releasing hormone analog, which has been widely used for treatment of spinocerebellar degeneration.…”

Cognitive Decline and Other Late-Stage Neurologic Complications in Cockayne Syndrome

“…While these symptoms are not specific to dementia, our participants' accelerated brain atrophy along with informant reported decline in cognition and behavior are core features of the NIA-AA criteria for all-cause dementia. 19 While tremors and neuropathy were found in the majority of our participants, with onset at younger ages consistent with previous reports, 1,15 neurocognitive/neuropsychiatric decline, strokes, and seizures tended to occur later in the disease course. Pathogenic variants in ERCC6 have generally been considered to be associated with more severe CS phenotypes.…”

A Case of ERCC6‐Related Cockayne Syndrome Presenting with Levodopa‐Responsive Tremor Syndrome

“…No definitive treatment has been introduced for CS. 8 A presentation of tremor and dysmetria responsive to treatments such as carbidopa-levodopa was reported in previous literature, 9 and our patient responded to botulinum toxin as well.…”

Nationwide survey of Cockayne syndrome in Japan: Incidence, clinical course and prognosis

“…reported that 9/21 adult patients had movement disorders (resting tremors in six cases and choreoathetosis in three cases) . Deep brain stimulation or oral carbidopa–levodopa was reported to be clinically effective in some CS patients with movement disorders (dystonia) . We also noted improvement of hand tremor in CS type 3 patients after addition of an oral synthetic thyrotropin‐releasing hormone analog, which has been widely used for treatment of spinocerebellar degeneration.…”