OTHER HYPERKINETIC MOVEMENT DISORDERS PART I

II. ABSTRACT

The hyperkinetic motor disorders are a heterogeneous group of conditions characterized by abnormal, excessive, involuntary movements. Although for many of these disorders the precise etiology and pathogenesis remain undefined, hemifacial spasm (HFS) and painful legs and moving toes syndrome (PLMTS) are well-described hyperkinetic motor disorders known to be associated with peripheral nerve damage. HFS typically presents with involuntary, unpredictable contractions of muscles innervated by the facial nerve. The most common cause of HFS is extrinsic compression of the ipsilateral facial nerve in the posterior fossa, usually by an anomalous or ectatic intracranial blood vessel. Involuntary movements in PLMTS involve the toes, occurring in association with pain or paresthesias; while the exact pathologic mechanism is unknown, electromyography usually reveals patterns suggestive of peripheral neuropathy or radiculopathy. The most effective treatment options for HFS are surgery or chemodenervation with botulinum toxin. Management of PLMTS is focused predominantly on pain management; satisfactory responses to chemodenervation are uncommon. This section will review the characteristic findings of HFS and PLMTS, and discuss approaches to diagnosis and treatment.

III. HEMIFACIAL SPASM

 a) Introduction

Hemifacial spasm (HFS) is a hyperkinetic motor disorder characterized by involuntary, unpredictable, progressive clonic or tonic contractions of the muscles innervated by the ipsilateral facial nerve. The predominant disability in HFS is involuntary eye closure that interferes with vision and is rather irritating to the patient.¹

Figure 1. Compression of the facial nerve (arrow) in the left cerebellopontine angle area by the left vertebral artery, shown on 2 MRIs: (A) coronal T2-weighted MRI; (B) maximal intensive projection (MIP). Microvascular compression of the ipsilateral facial nerve by an ectopic or atherosclerotic vessel is the most common cause of HFS. From Palacios et al.¹

The most common cause of HFS is mechanical compression of the ipsilateral facial nerve at its root exit zone (REZ) in the posterior fossa (Figure 1). This compression results in spontaneous (ectopic) generation of a neural impulse and lateral spread of excitation to nearby nerve fibers (ephaptic transmission), all without the mediation of a neurotransmitter.^{2, 3} In its earliest stages, HFS involves mainly the orbicularis oris muscle, but with chronicity there is gradual recruitment of other areas of the face supplied by the seventh nerve.

b) Epidemiology of HFS

The epidemiology of HFS has been investigated by several groups. A retrospective review of medical records over a 25-year period found the prevalence of HFS to be 14.5 and 7.4 per 100,000 in women and men, respectively, with an average age-adjusted annual incidence of new cases of 0.81 per 100,000 women and 0.74 per 100,000 men,⁴ thus indicating that while new cases arise comparably by gender, women bear a greater ongoing disease burden. Most patients present between 40 and 50 years of age.⁵

Prevalence of HFS appears to be higher in some Asian populations compared with Caucasians, but firm epidemiological data to support these observations is lacking.⁵ Most cases are sporadic. Familial cases have been reported, most likely reflecting a genetic predisposition to a vascular anomaly (see below).^6-10

Figure 2. Patterns of neurovascular compression (neurovascular conflict) implicated in hemifacial spasm. (A) Loop type: compression is created by the loop itself, with no contributing factors. (B) Arachnoid type: the vessel is tightly tethered to the nerve, due to thick arachnoid trabeculae between the vessel and the brainstem. (C) Perforator type: perforating arteries from the compressing vessel tether the vessel to the brainstem and cause compression. (D) Branch type: the nerve is caught between the compressing vessel and its branch. (E) Sandwich type: the nerve is sandwiched in between the 2 compressing vessels. (F) Tandem type: 1 vessel compresses another vessel, which compresses the nerve. There is no difference in postoperative outcome between the different patterns. R = tapered retactor; VII = facial nerve; VIII = vestibulocochlear nerve; BS = brainstem; CV = compressing vessel. Reprinted from Hyun.¹¹

Risk factors for HFS are those that potentially cause compression of the facial nerve (“neurovascular conflict”) near the REZ. The most common mechanism is compression by an aberrant or ectatic intracranial vessel, usually the anterior or posterior cerebellar artery or the vertebral artery (Figure 2). Others include tumors, arteriovenous malformations, bony abnormalities of the skull near the cerebellopontine angle, and meningioma.² Approximately 25% of asymptomatic normal controls will demonstrate neurovascular conflict on advanced imaging, suggesting the presence of additional, as yet unidentified, predisposing factors.⁵ Coexisting hypertension has been suggested as a potential predisposing factor, but confirmatory data are lacking.⁵

c) Clinical Features of HFS

Hemifacial spasm is nearly always unilateral; bilateral HFS is rare.^{2, 3} When bilateral, the spasms are always asynchronous on the two sides. Often, the lower eyelid is the site initially involved, followed by the cheek and perioral region. Involuntary eye closure severe enough to interfere with vision is the most common complaint. Other complaints may include facial paresthesias, eye irritation, tears, and photophobia.²

Contractions involving the periocular muscles are present in a majority of patients. Involuntary movements later extend to other ipsilateral muscles of expression, especially the zygomatic, perioral, chin, and frontalis musculature. Extension to muscle groups other than the orbicularis oculi may not be reported or noted by the patient, but it may be documented on careful examination.² In some cases, HFS extends to the periauricular region; some patients will report tinnitus-like phenomena (clicking, ticking) or impaired hearing. Auditory complaints may or may not be synchronous with facial contractions. Tongue discomfort has been reported.²

Symptoms are often exacerbated by stress, anxiety, and fatigue. Voluntary facial movements may also intensify the symptoms. Relaxation and alcohol are reported as the most common alleviating factors, but symptoms often persist during sleep.² In its extreme form, HFS may interfere with social function, job performance, driving, and personal safety.

d) Diagnosis of HFS

Apart from twitching, the neurological exam for HFS is usually unremarkable.² Coexistence of HFS with other neurological disorders, such as trigeminal neuralgia or Bell’s palsy, either on exam or by history, seems to be coincidental.²

The principal diagnostic dilemma is differentiating HFS from psychogenic spasm, myokymia, blepharospasm, tic, and tardive dyskinesia; however, clinical distinction is usually possible with careful examination. HFS is nearly always unilateral, and involvement of the periorbital and zygomatic musculature is often present. Blepharospasm is characterized by dystonic movements that are virtually always bilateral, and in pure form involves the orbicularis muscle exclusively. Tics are rapid, stereotyped movements that commonly involve the face and limbs, are often preceded by a premonitory urge, and may be voluntarily suppressed for a period of time (Table 1).⁵

Table 1. Differential Diagnosis of Involuntary Facial Movements⁵

The utility of advanced imaging in diagnostic algorithms is unclear,² as the diagnosis is often made on clinical grounds and anomalies consistent with neurovascular conflict may not be apparent in all patients in HFS. Patients with atypical features or symptoms such as extensive facial numbness or paresis, loss of corneal reflex, or loss of hearing, should undergo imaging to exclude an intracranial space-occupying lesion.⁵ Because the onset in more than 90% of cases of HFS is in the upper face, involvement of the lower face as the initial manifestation should suggest the possibility of pathology in the region of the brainstem.²

e) Treatment of HFS

Treatment options for HFS include medication, surgical microvascular decompression, and intramuscular injections of BoNT. Pharmacological agents include carbamazepine, clonazepam, baclofen, and gabapentin. However, pharmacological treatment is consistently unsatisfactory: benefits are mild, inconsistent, and rarely long-lasting.² 

Surgical Microvascular Decompression

Microvascular decompression is an effective surgical intervention for HFS, relieving the most common patterns of neurovascular conflict (Figure 2). Hyun et al prospectively enrolled 1174 patients with HFS who underwent microvascular decompression.¹¹ At 1-year follow-up, 94% were categorized as clinically cured and 6% had residual spasms.¹¹ The onset of benefit followed different temporal patterns, with 76.7% experiencing complete relief in the early postoperative period (within 3 months) and 94.9% reaching complete relief by 12 months: patients without cure at 12 months were unlikely to experience a cure.¹¹ Major postoperative complications included transient hearing loss in 31 (2.6%), permanent hearing loss in 13 (1.1%), transient facial weakness in 86 (7.3%), permanent facial weakness in 9 (0.7%), cerebrospinal fluid leak in 3 (0.25%), and cerebellar infarction or hemorrhage in 2 (0.17%).¹¹

If benefits are obtained with microvascular decompression, they tend to be durable. A retrospective review of the incidence and timing of symptom recurrence following surgery found that approximately 10% of patients develop recurrent spasm and 86% of recurrences develop within 2 years of surgery. Patients who remain symptom free for 2 years after surgery have only a 1% chance of recurrence.¹² A more recent retrospective review of a single-center experience with microvascular decompression showed 86% of patients were spasm free at 10 years post-surgery.¹³

Role of Botulinum Neurotoxin

Chemodenervation with BoNT is becoming more common in the treatment of HFS, since it is so effective and many patients shy away from surgery and its attendant risk of postoperative complications.² Muscles commonly injected to treat HFS are the orbicularis oculi, corrugator, frontalis, zygomaticus major, buccinators and depressor anguli oris (Figure 3); the orbicularis oris is avoided to prevent paralysis of the mouth, which would produce further disability.¹⁴

Figure 3. Common botulinum toxin injection sites for management of hemifacial spasm.

Good data supporting the use of botulinum toxin for management of HFS is available only for BoNT-A. A recent systematic review of randomized trial data confirms that BoNT-A is safe and effective for treatment of HFS, achieving benefits in 76% to 100% of patients.¹⁵  The average latency to improvement is 5 days, the average duration of improvement is 12-20 weeks, and remission from 1 to 9 years has been reported in subgroups of patients after 1 to 6 injections. About 95% of patients can expect marked to moderate improvement with BoNT-A  treatment.²  A prospective, descriptive study evaluated 158 patients who received a median of four treatments. Long-term results (from first to twelfth treatment) showed mean peak improvement ranged from 72.7% to 80.1%, with duration of improvement from 2.6 to 3.7 months.¹⁶  The American Academy of Neurology assessment of BoNT for treatment of movement disorders recommends considering BoNT for HFS.¹⁷

The most commonly reported adverse events with BoNT-A  given for HFS include ptosis, lid weakness, dry eye (as well as teary eyes), diplopia, and facial weakness. Remote side effects are infrequent. All side effects are transient, reversible, and rarely disabling.^{2, 17}

SKIP TO PAINFUL LEGS AND MOVING TOES SYNDROME

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IV. PAINFUL LEGS AND MOVING TOES SYNDROME (PLMTS)

a) Introduction

Painful legs and moving toes syndrome (PLMTS) is an enigmatic, rare condition in which the patient presents with involuntary writhing, clawing, or fanning movements of the toes associated with painful legs. First described in 1971, identification of subsequent cases has allowed for modification of the description to include variants presenting without any pain at all.^{1, 2}  There is also a similar syndrome in the upper extremity with painful arms and moving fingers.

b) Epidemiology of PLMTS

PLMTS is rare, and no reliable data have been compiled upon which to base prevalence statistics. In a recent review of 4780 patients referred to a specialty movement disorder clinic, only 14 cases of PLMT and its variants were identified. Onset is between the second and seventh decades of life.  The pathogenesis of PLMTS is unknown. There is clear relevance for the peripheral nerve or root injury, but it is likely that the movements themselves are generated centrally.¹

c) Diagnosis of PLMTS

Limb movements may consist of flexion/extension, adduction/abduction, fanning, and clawing of toes, fingers, or both. Movements can be bilateral or unilateral, and pain tends to precede movements. The most common sensory symptoms are burning pain; numbness; or sharp, shooting, dull, or achy pain. There are no specific biochemical or advanced brain-imaging findings, but electromyography typically reveals patterns consistent with neuropathy or radiculopathy.¹

d) Treatment of PLMTS

Pain management is the key focus; patients without pain usually do not need treatment. Commonly prescribed interventions have included gabapentin, nortriptyline, amitriptyline, analgesic patches, quinine, hydrocodone, acetaminophen, ibuprofen, baclofen, diazepam, carbamazepine, epidural transcutaneous stimulation, and BoNT.^{1, 3} Case reports describing the effect of BoNT note improvement in pain symptoms as well as lessening of involuntary movement; the mechanism by which BoNT interferes with nociception is unclear.^{4, 5} Successful response to BoNT, however, is not common.

REFERENCES

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