eMedicine Specialties > Neurology > Movement and Neurodegenerative Diseases
Hallervorden-Spatz Disease: Treatment & Medication
Updated: Dec 1, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Treatment remains directed toward symptomatic findings. Systemic chelating agents such as desferrioxamine have been used in an attempt to remove excess iron from the brain, but these have not proved beneficial.
- Dystonia is the most prominent and disabling symptom and may respond to a modest extent to dopaminergic agents such as levodopa and bromocriptine (a dopamine agonist). Other dopamine agonists such as ropinirole or pramipexole can be considered, although no formal studies have been conducted on their efficacy in HSD.
- Anticholinergics such as trihexyphenidyl may be used when dopaminergic agents are not helpful. However, these medications bring only transient relief for dystonia, and physical therapy is often of limited benefit.
- Botulinum toxin can be injected into severely affected muscles to relieve dystonia.
- Continuous intrathecal baclofen infusion has been tried for refractory generalized dystonia without much success.
- Stereotactic pallidotomy and bilateral thalamotomy occasionally have been tried for patients with severe dystonia, resulting in partial relief of symptoms.24
- Tremor in patients with HSD responds best to dopaminergic agents. The anticholinergic agent benztropine helps both rigidity and tremor.
- Benzodiazepines have been tried for choreoathetotic movements.
- Hypertonia is usually a combination of rigidity and spasticity and may be difficult to treat.
- Dopamine agonists and anticholinergics may help reduce rigidity.
- Baclofen in moderate doses relieves the stiffness and spasms and can reduce dystonia.
- Symptoms such as drooling and dysarthria can be troublesome.
- Treat excessive drooling with a medication such as methscopolamine bromide.
- Dysarthria may respond to medications used for rigidity and spasticity.
- Speech therapy also may be useful, and computer-assisted devices may be used in patients with advanced cases.
- Gastrostomy feeding may be necessary in advanced cases of dysphagia.
- Dementia is progressive, and no treatment has proved clearly beneficial.
- A multidisciplinary team approach involving physical, occupational, and speech therapists may be needed in selected patients with a protracted course to improve functional skills and communication.
Surgical Care
As dystonia is a prominent feature in this condition, the globus pallidus has been a target for surgical treatment. Stereotactic pallidotomy and bilateral thalamotomy have occasionally been tried for patients with severe dystonia, resulting in partial relief of symptoms.24 Deep brain stimulation of the globus pallidus has been used in these patients with promising results.25,26
Intrathecal baclofen infusion is an additional treatment modality for refractory generalized dystonia.
Medication
Medications are tailored to treat specific aspects of the disease (see Medical Care).
Antiparkinson agents
These agents reduce morbidity associated with dopamine deficiency.
Levodopa/carbidopa (Sinemet, Sinemet CR)
Given together with carbidopa (a decarboxylase inhibitor) to prevent breakdown of levodopa and increase bioavailability. Decreases need for large doses of levodopa to achieve adequate brain dopamine levels. Often used when symptom control with selegiline alone is insufficient. CR formulation can help prevent on/off phenomenon in some patients. Sinemet tab available in 4:1 ratio (Sinemet 100/25) and 10:1 ratio (Sinemet 100/10 and 250/25) of levodopa to carbidopa. Sinemet CR tab contains 4:1 ratio of levodopa to carbidopa (100/25 or 200/50); daily dosage of Sinemet CR must be determined by careful titration.
Adult
1 tab Sinemet CR 100/25 PO bid initially; in patients who require more levodopa, daily dose of 1-2 tab bid generally well tolerated
Pediatric
Not established
Hydantoins, pyridoxine, phenothiazine, and hypotensive agents may decrease effects; antacids and MAOIs increase toxicity
Documented hypersensitivity; narrow-angle glaucoma; malignant melanoma; undiagnosed skin lesions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Certain adverse CNS effects (eg, dyskinesias) may occur at lower dosages and earlier in therapy with SR form; caution in patients with history of myocardial infarction, arrhythmias, asthma, or peptic ulcer disease; sudden discontinuation of levodopa may cause worsening of Parkinson disease; high-protein diets should be distributed throughout day to avoid fluctuations in levodopa absorption
Bromocriptine (Parlodel)
Semisynthetic ergot alkaloid derivative; strong dopamine D2-receptor agonist; partial dopamine D1-receptor agonist; FDA approved as adjunct to levodopa/carbidopa, but less effective than other dopamine agonists.
May relieve akinesia, rigidity, and tremor associated with Parkinson disease. Stimulates dopamine receptors in corpus striatum.
Approximately 28% absorbed from GI tract and metabolized in liver. Approximate elimination half-life is 50 h with 85% excreted in feces and 3-6% eliminated in urine. Initiate at low dosage; slowly increase dosage to individualize therapy. Maintain dosage during introductory period. Assess dosage titration every 2 wk. Gradually reduce dose in 2.5-mg decrements if severe adverse reactions occur.
Adult
1.25 mg PO bid initially; increase by 2.5 mg/d q2-4wk to 10-40 mg/d; not to exceed 100 mg/d
Pediatric
Not established
Ergot alkaloids may increase toxicity; amitriptyline, butyrophenones, imipramine, methyldopa, phenothiazines, reserpine may decrease effects
Documented hypersensitivity; ischemic heart disease; peripheral vascular disorders
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in renal or hepatic disease
Anticholinergics
These agents are thought to work centrally by suppressing conduction in the vestibular cerebellar pathways. They may have an inhibitory effect on the parasympathetic nervous system.
Trihexyphenidyl (Artane, Trihexy)
Centrally acting anticholinergic that tends to diminish muscle spasms.
Adult
1 mg PO on day 1 initially; 2 mg on day 2; then increase by 2 mg q3-5d to 6-10 mg qd
Pediatric
Not established
Amantadine may increase anticholinergic side effects that disappear when dose reduced; may decrease haloperidol serum concentration, resulting in worsening of schizophrenic symptoms; may reduce pharmacologic/therapeutic actions of phenothiazines
Documented hypersensitivity; glaucoma; peptic ulcers; pyloric or duodenal obstruction; stenosing prostatic hypertrophy; bladder neck obstructions; achalasia; toxic megacolon
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Dose adjustment may be required in geriatric patients; caution in patients with tachycardia, cardiac hypotension, prostatic hypertrophy, arrhythmias, hypertension, any tendency toward urinary retention, liver or kidney disorders, or obstructive disease of GI or GU tract; if dry mouth severe and impairs swallowing or speaking, or if loss of appetite and weight occurs, reduce dosage or discontinue medication temporarily
Benztropine (Cogentin)
By blocking striatal cholinergic receptors, may help in balancing cholinergic and dopaminergic activity in striatum.
Adult
0.5-1 mg/d PO initially; then increase by 0.5 mg q5-6d to 0.5-6 mg PO qd; not to exceed 6 mg/d
Pediatric
Not established
Decreases effects of levodopa; increases effects of narcotic analgesics, phenothiazines, quinidine, tricyclic antidepressants, and anticholinergics
Documented hypersensitivity; glaucoma, angle-closure; stenosing peptic ulcers; prostatic hypertrophy; bladder neck obstructions; myasthenia gravis; pyloric or duodenal obstruction; achalasia (megaesophagus); megacolon
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May exacerbate hypertension, tachycardia, cardiac arrhythmias, liver or kidney disorders, hypotension, prostatic hypertrophy, urinary retention, or obstructive disease of GI/GU tract; extrapyramidal reactions, resulting from phenothiazine treatment in psychiatric patients, may cause toxic psychosis
Scopolamine (Transderm Scop Patch)
Blocks action of acetylcholine at parasympathetic sites in smooth muscle, secretory glands, and CNS. Antagonizes histamine and serotonin action.
Adult
1 patch (1.5 mg) 4 h before expected time of symptoms
Pediatric
Not established
May decrease antipsychotic effectiveness and increase anticholinergic side effects of phenothiazines—adjust dosages as necessary; tricyclic antidepressants may increase anticholinergic side effects (eg, dry mouth, constipation, urinary retention) owing to additive effect (tricyclic antidepressants with less anticholinergic activity may be beneficial)
Documented hypersensitivity; primary glaucoma (including initial stages); pyloric obstruction; toxic megacolon; hepatic disease; paralytic ileus; severe ulcerative colitis; renal disease; obstructive uropathy; myasthenia gravis
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in the elderly because of increased incidence of glaucoma; large doses may suppress intestinal motility and precipitate or aggravate toxic megacolon; anticholinergics may aggravate hiatal hernia associated with reflux esophagitis; patients with prostatism can have dysuria and may require catheterization; use cautiously in patients with asthma or allergies; reduction in bronchial secretions can lead to inspissation and formation of bronchial plugs
Benzodiazepines
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 and other inhibitory transmitters.
Adult
0.5 mg PO bid initially; increase by 0.5 mg q3-5d to 0.5-5 mg/d; maximum dose varies depending on tolerance to adverse effects
Pediatric
Not established
Phenytoin and barbiturates may reduce effects; CNS depressants increase toxicity
Documented hypersensitivity; severe liver disease; acute narrow-angle glaucoma
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in chronic respiratory disease or impaired renal function; withdrawal symptoms can result from abrupt discontinuation of medication
Neuromuscular blocker agents
These agents produce symptomatic improvement in strength, autonomic symptoms, or both in some patients.
Botulinum toxin type A (BOTOX)
Binds to receptor sites on motor nerve terminals and inhibits release of acetylcholine, which in turn inhibits transmission of impulses in neuromuscular tissue.
Adult
25-400 U IM, depending on site of injection; not to exceed 400 U per visit or 50 U per injection site
Pediatric
Total body dose per visit not to exceed <12 U/kg or 400 U IM; dose per large muscle per visit not to exceed 3-6 U/kg IM; dose per small muscle per visit not to exceed 1-2 U/kg; dose per injection site not to exceed 50 U
Aminoglycosides or drugs that interfere with neuromuscular transmission may potentiate effects
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Do not exceed recommended dosages and frequencies of administration; presence of antibodies to botulinum toxin type A may reduce effects of therapy
More on Hallervorden-Spatz Disease |
| Overview: Hallervorden-Spatz Disease |
| Differential Diagnoses & Workup: Hallervorden-Spatz Disease |
 Treatment & Medication: Hallervorden-Spatz Disease |
| Follow-up: Hallervorden-Spatz Disease |
| Multimedia: Hallervorden-Spatz Disease |
| References |
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Further Reading
Keywords
HSD, neurodegeneration with brain iron accumulation type 1, NBIA-1, Hallervorden-Spatz disease, progressive extrapyramidal dysfunction, dementia, PANK2 gene, pantothenate kinase-associated neurodegeneration, PKAN
