Corticobasal Syndrome and Corticobasal Degeneration Medication

Updated: Dec 04, 2019
  • Author: Alexander Pantelyat, MD; Chief Editor: Selim R Benbadis, MD  more...
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Medication

Medication Summary

Unfortunately, no regimen is reported to be highly effective in reversing or slowing the motor or cognitive symptoms of corticobasal syndrome (CBS) or other clinical corticobasal degeneration (CBD) phenotypes. [35]  Cholinesterase inhibitors can be tried; these have been reported to benefit patients with other tauopathies. [36] Medications for Parkinson disease, particularly levodopa at doses of 900–1,500 mg/day, may improve symptoms such as tremor to some extent in some patients and should be tried in everyone presenting with a component of parkinsonism. [17, 37]  Botulinum toxin injections may improve dystonia, blepharospasm/eyelid opening apraxia and sialorrhea. Clonazepam may improve myoclonus and tremor (in 23% per one study), but its use is limited by sedation and levetiracetam may be of benefit for myoclonus as well. [17, 38] Antidepressants such as sertraline, escitalopram, and venlafaxine should be considered for all patients with depression and anxiety in the context of CBD. When initiating antidepressants, patients should be monitored for clinical worsening of symptoms, behavior changes, and suicidality. [39] They should never be stopped abruptly, but gradually tapered off – during this time patients should be monitored for withdrawal symptoms, including agitation, emotional lability, nervousness or irritability. Sleep quality may be improved with melatonin up to 15mg used nightly; trazodone may be considered as well if melatonin is ineffective.

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Benzodiazepines

Class Summary

Useful for the management of myoclonus. By binding to specific receptor sites, these agents appear to potentiate the effects of GABA and facilitate inhibitory GABA neurotransmission and other inhibitory transmitters.

Clonazepam (Klonopin)

Suppresses muscle contractions by facilitating inhibitory GABA neurotransmission. Can suppress myoclonus and also improve tremor.

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Neuromuscular Blocking Agents, Toxins

Class Summary

These may be useful for the management of dystonia, especially painful dystonia. Botulinum toxin can inhibit transmission of impulses in neuromuscular tissue.

OnabotulinumtoxinA (Botox)

Useful in reducing excessive, abnormal muscular contractions. Binds to receptor sites on motor nerve terminals and after uptake inhibits release of acetylcholine, blocking transmission of impulses in neuromuscular tissue. Thought to also exert pain-relieving effects through centrally acting mechanisms (uptake into CNS).

Strongly advise having patients monitor and document their response to injections weekly (using a diary or spreadsheet) to assess for satisfactory response and side effects.

Increase doses 1.5 to 2 times over previously administered dose for patients who experience incomplete paralysis of target muscle. Doses of 100-800 units are administered, depending on the number of target symptoms/sites and patient tolerance of higher doses.

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Cholinesterase Inhibitors

Class Summary

Galantamine may reduce symptoms of primary progressive aphasia in cortical basal ganglionic degeneration. Other cholinesterase inhibitors may also be effective, although supportive data are preliminary and only available for galatamine at this time.

Galantamine (Razadyne, Razadyne ER)

Galantamine is a competitive and reversible inhibitor of acetylcholinesterase. While the mechanism of action is unknown, it may reversibly inhibit cholinesterase, which may, in turn, increase concentrations of acetylcholinesterase available for synaptic transmission in the CNS and enhance cholinergic function. There is no evidence that acetylcholinesterase inhibitors alter the course of underlying dementia.

Rivastigmine (Exelon)

Rivastigmine is a competitive and reversible acetylcholinesterase inhibitor. Although its mechanism of action is unknown, it may reversibly inhibit cholinesterase, which may, in turn, increase concentrations of ACh available for synaptic transmission in the CNS and thereby enhance cholinergic function. Rivastigmine’s effect may lessen as the disease process advances and fewer cholinergic neurons remain functionally intact. May improve recent memory and (less likely) overall cognition.

Donepezil (Aricept)

Noncompetitively inhibits centrally active acetylcholinesterase, which may increase concentrations of ACh available for synaptic transmission in CNS. May improve recent memory.

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Antidepressants

Class Summary

Selective serotonin reuptake inhibitors (SSRIs) are greatly preferred over the other classes of antidepressants. Because the adverse-effect profile of SSRIs is less prominent than the profiles of other drugs, improved compliance is promoted. SSRIs do not have the cardiac arrhythmia risk associated with tricyclic antidepressants. Arrhythmia risk is especially pertinent in overdose, and suicide risk must always be considered when one treats a child or adolescent with a mood disorder.

Escitalopram (Lexapro)

Selective serotonin reuptake inhibitor (SSRI) and S-enantiomer of citalopram. Used for the treatment of depression. Mechanism of action is thought to be potentiation of serotonergic activity in central nervous system resulting from inhibition of CNS neuronal reuptake of serotonin. Onset of depression relief may be obtained after 1-2 wk, which is sooner than other antidepressants. Use at standard recommended doses.

Sertraline (Zoloft)

Is an SSRI used to treat impulse-control problems or underlying illness. It selectively inhibits presynaptic serotonin reuptake with minimal or no effect in reuptake of norepinephrine or dopamine. Use at standard recommended doses.

Trazodone (Desyrel, Desyrel Dividose, Oleptro)

Trazodone can be tried, with starting doses of 25 to 50 mg BID-TID (up to 150 mg total per day as a starting dose). This can be increased by 25-50 mg/day every 3–4 days to a maximum dose of 400 mg daily. Side effects include dizziness, somnolence, fatigue, constipation, diarrhea, nervousness, dream disorders, blurred vision, and hypotension.

Venlafaxine (Effexor, Effexor XR)

Venlafaxine is structurally unrelated to other available antidepressants. It inhibits serotonin reuptake at select receptors, as well as the reuptake of norepinephrine.

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NMDA Antagonists

Class Summary

Glutamate release inhibition and glutamate receptor blockade are alternatives to potentiating D2 receptors in the indirect pallidal outflow pathway by reducing the glutamate-related excitatory circuit in this outflow pathway.

Memantine (Namenda)

This agent, approved for the treatment of Alzheimer disease in the US, may be of benefit for CBS since 20-30% of patient will have AD pathology.

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Antiparkinson Agents, Dopamine Agonists

Class Summary

A dopamine agonist must stimulate D2 receptors if it is to offer clinical benefit. D2 receptor blockade might cause neuroleptic malignant syndrome by removing tonic inhibition from the sympathetic nervous system or more directly by neuroleptic agents

Amantadine (Gocovri, Osmolex ER)

Amantadine inhibits N-methyl-D-aspartic acid (NMDA) receptor-mediated stimulation of acetylcholine release in the striatum. This agent may enhance dopamine release, inhibit dopamine reuptake, stimulate postsynaptic dopamine receptors, or enhance dopamine receptor sensitivity.

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Decarboxylase Inhibitors

Class Summary

Dopamine agonists directly stimulate postsynaptic dopamine receptors to provide benefit against symptoms of of the diseae. In order for a dopamine agonist to offer clinical benefit, it must stimulate D2 receptors. The role of other dopamine receptor subtypes is currently unclear.

Levodopa/carbidopa (Sinemet, Ritary, Duopa)

Lack of robust response to this medication in the context of CBS supports the diagnosis of CBD, although the same is generally true of PSP; an empiric trial, titrated to relatively high dose (minimum of 900- up to 1,500 mg daily for at least 1 month), is recommended in every patient.

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Anticonvulsants

Class Summary

Many anticonvulsants are used to alleviate painful dysesthesias, which frequently accompany peripheral neuropathies. Although they have many different mechanisms of action, their use for alleviating neuropathic pain probably depends on their general tendency to reduce neuronal excitability.

Levetiracetam (Keppra, Keppra XR, Roweepra XR, Spritam)

Has been used successfully for myoclonus in CBS. Use limited by irritability, particularly in patients with a history of psychiatric disorders.

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