Clinical manifestations

Presentation and course

	• Drop attacks are sudden falls without loss of consciousness that are not precipitated by a specific stimulus, occur with abrupt onset and without warning, and are followed by a rapid return to baseline.
	• The term "drop attack" has been broadened to the point where its conventional usage is not clinically useful.
	• Clinical criteria for drop attacks are provided.

Drop attacks are sudden falls without loss of consciousness that are not precipitated by a specific stimulus, occur with abrupt onset and without warning, and are followed by a rapid return to baseline (59). Initially, these events were described in otherwise healthy elderly people (59), but the term “drop attack” has subsequently been used to encompass a wide variety of sudden falls with or without existing conditions known to increase the risk of falls, with or without provocation by a specific stimulus, with or without loss of consciousness, and with or without significant baseline abnormalities. Therefore, as often used, "drop attack" says little more than someone had a fall. Such vague use should be avoided. Clinical criteria for drop attacks are outlined in Table 1.

Table 1. Clinical Criteria for Drop Attacks

Sudden falls while standing or walking
Onset
	• abrupt • no aura or warning • not provoked by specific stimulus
Event
	• brief (seconds to a few minutes) • no loss of consciousness • no evidence of seizure (eg, tonic or clonic activity) • may be accompanied by transient neurologic signs and symptoms
Post-event
	• fully alert • not confused • rapidly returns to baseline • may have transient difficulty standing
Baseline
	• no severe leg weakness, ataxia, postural instability, or sensory loss

Tumarkin otolithic catastrophes (vestibular drop attacks). Tumarkin otolithic catastrophes (or crises) are a specific category of drop attacks that warrant further consideration. They are now sometimes referred to as vestibular drop attacks (53). Tumarkin crises cause drop attacks without associated autonomic or neurologic symptoms in patients with severe vestibular disease, usually due to Ménière disease (67; 03; 24; 43; 02; 23; 22; 25; 28; 65; 47; 49; 20; 68; 50; 52; 51; 53; 70; 63). Rarely vestibular drop attacks may be the presenting sign of Ménière disease (02; 17), and ultimately about 8% of patients with Meniere disease develop vestibular drop attacks (68; 26). Patients frequently report the sensation of being pushed, thrown, or knocked to the ground (67; 02; 22). Many have a subjective tilt of the environment concurrently with the fall (22). Although occurring in patients with Ménière disease, vestibular drop attacks are not generally associated with the simultaneous occurrence of symptoms of typical attacks of Ménière disease (ie, aural fullness, tinnitus, fluctuating hearing loss, or vertigo) (67). However, a subset of patients may have transient vertigo after a vestibular drop attack (29). Typically, patients with vestibular drop attacks can stand up immediately after a fall, whereas patients with drop attacks from other causes may require several minutes to stand independently. Similar events may occur in patients without Ménière syndrome, but with a personal and family history of migraine and with typical migraine triggers for their drop attacks (eg, alcohol, lack of sleep, emotional stress, and menses) (27; 22). Patients with Ménière disease who develop Tumarkin attacks are more disabled, have more severely impaired hearing, especially at low frequencies, and experience autonomic symptoms that are more severe and more frequent than those without Tumarkin attacks (49; 51; 70; 08; 26). They are also more fearful and anxious, self-report greater impairment in work ability, and are more likely to have to apply for work-related disability pensions than Ménière syndrome patients without Tumarkin attacks (51). Migraine is common in patients with vestibular drop attacks (53). Some patients with Tumarkin attacks can also have syncope (50; 52; 51; 26).

Prognosis and complications

Those with baseline significant neurologic findings, cardiac arrhythmias, and congestive heart failure have a worse prognosis (37). Patients with an isolated drop attack who have unrevealing medical and neurologic evaluations have a favorable long-term outcome (37).

Injuries are common with drop attacks because the falls are unexpected and rapid, with inadequate opportunity for self-protective responses. Long-term prognosis depends on the underlying condition. In a case series of 15 patients with Ménière disease, drop attacks (otolithic crises) were complicated either by severe head trauma (n = 1) or various fractures (n = 4) (29).

Some previous studies of prognosis have included patients with cardiovascular syncope, epilepsy, and other conditions that would not meet the criteria for true drop attacks.

Clinical vignette

A 70-year-old man presented with drop attacks (23). The events occurred without warning and were characterized by a feeling of being pushed to the left with a sudden loss of postural tone and abrupt falls, but no loss of consciousness, no associated focal neurologic findings, and no residual weakness. He had four falls over the previous year. He had a 2-year history of recurrent vertigo several times a week, lasting from 10 minutes to several hours, but without meeting the criteria for Ménière syndrome (ie, no aural fullness, change in tinnitus, or fluctuation in hearing loss accompanying vertigo). He also had a history of (sudden?) profound right-sided hearing loss 8 years previously. Neurologic examination, MRI with gadolinium, carotid ultrasound, and electroencephalography were unrevealing. A presumptive diagnosis of atonic seizures was made, but there was no improvement after treatment with phenytoin. Audiograms demonstrated a profound right-sided sensorineural hearing loss, and caloric testing demonstrated a complete right caloric paresis. A presumptive diagnosis of “vestibular Ménière disease” was apparently made and he was treated with a low-salt diet and diuretics without benefit. He ultimately underwent a right transmastoid labyrinthectomy and was able to walk unassisted by 3 weeks after surgery. He remained free of vertigo and drop attacks 3 years after surgery.

Biological basis

	• Although various localizations for drop attacks are possible, lower brainstem or spinal cord structures are most commonly implicated.
	• In patients with Ménière disease, vestibular drop attacks (Tumarkin “otolithic catastrophes”) probably result from mechanical deformation of the otolithic membrane of the utricle or saccule.
	• Drop attacks generally indicate transient impairment of bilateral central nervous system structures involved in maintenance of postural muscle tone and balance.

Anatomic localization

Although various localizations for drop attacks are possible, lower brainstem or spinal cord structures are most commonly implicated. In patients with Ménière disease, vestibular drop attacks (Tumarkin “otolithic catastrophes”) probably result from mechanical deformation of the otolithic membrane of the utricle or saccule (67; 02; 65; 20). Less commonly, hemispheric motor outflow tracts (eg, acute hydrocephalus with third ventricular cysts, or bilateral anterior cerebral artery ischemia) have been implicated. Transient dysfunction of these areas can disrupt muscle tone bilaterally without affecting consciousness.

Pathophysiology

Drop attacks generally indicate transient impairment of bilateral central nervous system structures involved in maintenance of postural muscle tone and balance. In patients with cryptogenic drop attacks, a delay in long-loop (transcortical) reflexes may produce inadequately rapid adjustments in postural tone to maintain the erect posture under certain circumstances (14).

Studies employing audiometry, vestibular evoked myogenic potentials (VEMP), and MRI have identified endolymphatic hydrops with involvement of the otolith system as responsible for vestibular drop attacks in Ménière disease (26).

In some patients, drop attacks may represent a form of functional neurologic disorder, and such individuals may have additional precipitating factors identified, including situational triggers, high levels of stress, and dissociation (56).

Epidemiology

There have been no epidemiologic studies of drop attacks.

Vestibular drop attacks are a common phenomenon in Ménière disease, occurring even in mild Ménière disease. The frequency of vestibular drop attacks in Ménière disease leading to a fall has varied from 3% to 19%, with a pooled frequency of 8% (95% CI 4 to 12%) in hospital-based studies (68; 26). In studies that included attacks with postural perturbation, tripping, and near-to-fall events, prevalence ranged from 50% to 72%. Comorbidity with migraine increased the likelihood of vestibular drop attacks in Ménière disease. In a large series of 375 patients with Ménière disease at a tertiary, hospital-based, neuro-otology clinic, vestibular drop attacks were a presenting feature of Ménière disease in 3% of cases (17).

Differential diagnosis

Confusing conditions

In elderly patients with sudden falls and presumed drop attacks, the absence of a history of loss of consciousness is unreliable (09). More than two thirds of such patients are in fact found to have forms of cardiovascular syncope, including carotid sinus syndrome, orthostatic hypotension, and vasovagal syncope (09; 64). Other causes in elderly patients include vestibular disorders (28) and cerebrovascular disorders.

Drop attacks can be confused with the falls caused by atonic seizures (42), cataplexy and other stimulus-induced drop episodes, movement disorders (eg, asterixis, chorea, myoclonus) (36), and syncope. In children and young adults, it is important to distinguish spontaneous drop attacks with preserved consciousness from atonic seizures (with transient loss of consciousness) and stimulus-induced drop episodes (SIDEs). In older adults, it is particularly important to distinguish spontaneous drop attacks from syncope (for which the loss of consciousness may be transient and unrecognized).

So-called "epileptic drop attacks." The term “epileptic drop attacks” is a misnomer, as these events are generalized seizures with brief loss of consciousness. So-called epileptic “drop attacks” occur with myoclonic-atonic seizures (also called astatic or myoclonic-astatic seizures), Lennox-Gastaut syndrome, or other symptomatic generalized epilepsies associated with brief rapidly generalized seizures manifesting transient loss of consciousness and sudden atonic falls without protective reflexes (48; 11; 44; 45; 12; 30; 15; 66; 33; 55). The loss of muscle tone is brief and may include head drop, jaw droop, dropping of a limb, or loss of all muscle tone and a fall (often with resulting head and facial injuries). Epileptic “drop attacks” occur most commonly in young children but may begin in adolescence and rarely in adults. Such epileptic falls are physically dangerous and are often refractory to medical and surgical therapy. Interictal electroencephalograms are usually abnormal and may include slow spike-wave complexes, rhythmic slow activity, polyspike and wave activity, temporal or frontal spikes, and bilateral synchronous spike activity during sleep.

Stretch syncope. Stretch syncope may be difficult to distinguish from epilepsy (58). Episodes are initiated with stretching associated with neck torsion and breath holding, which may be followed by loss of consciousness and in more prolonged episodes by asymmetric, recurrent facial and upper limb jerks. Stretching may be associated with sinus tachycardia, followed by rhythmic generalized slow wave abnormalities on EEG in attacks with associated impairment of consciousness. Transcranial Doppler studies showed a marked drop in middle cerebral artery perfusion during the episodes.

Stimulus-induced drop episodes (SIDEs) in Coffin-Lowry syndrome. Coffin-Lowry syndrome is a rare X-linked genetic disorder that was first described by Grange S Coffin and colleagues in 1966, with subsequent reports by Martinelli and Campailla in 1969 (in Italian and largely unrecognized until later), Coffin and Siris in 1971, and Brian Lowry and colleagues in 1971 (07; 35; 06; 32; 05). Coffin-Lowry syndrome is classically associated with moderate-to-severe mental retardation, characteristic facial features, skeletal deformities, and tapering fingers in males. Females are much more mildly and variably affected.

A stimulus-induced paroxysmal disorder was described in up to 10% patients with Coffin-Lowry syndrome, characterized by a sudden loss of muscle tone induced by unexpected tactile or auditory stimuli (38; 39; 04; 10; 40; 60; 46; 18; 16; 01; 41; 13; 54; 21; 57). These events were variously termed cataplexy, nonepileptic collapses with atonia, exaggerated startle responses, hyperekplexia, and stimulus-induced drop episodes (SIDEs). Such stimulus-induced drop episodes are not "drop attacks" per se, certainly as strictly defined, because they are evoked by a stimulus. These episodes typically begin from mid-childhood to adolescence. Unexpected tactile or auditory stimuli or excitement triggers a brief collapse without loss of consciousness. The affected individual is back to normal within seconds. The likelihood of a drop episode is related to the individual's level of anxiety or apprehension, so a fear of falling becomes self-fulfilling. The drop episodes increase in frequency and severity over time, often becoming debilitating, as the individual becomes afraid to stand for fear of falling down (and in this way resembling phobic postural vertigo). Many remain ambulatory while at home but use a wheelchair elsewhere for safety.

Associated or underlying disorders

Cryptogenic drop attacks are relatively common, represent a large proportion of drop attacks in case series, and mainly affect women (61). Data suggest that cryptogenic drop attacks overlap with functional neurologic disorders (19). Specifically, cryptogenic drop attacks are: (1) associated with high frequency of comorbid functional somatic and functional neurologic disorders; (2) commonly accompanied by prodromal dissociative symptoms; and (3) in some cases, there is a clear relationship with prior or subsequent dissociative (nonepileptic) attacks (19).

An autoimmune basis has also been proposed to account for some cases with cryptogenic drop attacks. Drop attacks have been reported in two women with facio-brachio-crural dystonic episodes associated with antibodies to leucine-rich glioma-inactivated 1, presumably an autoimmune encephalitis (34). In both cases, prolonged EEG monitoring and brain MRI studies were normal, and neither responded to conventional anticonvulsants. One case apparently responded to corticosteroid treatment with intravenous methylprednisolone, whereas the other improved spontaneously over 6 months.

Orthostatic hypotension may cause both traumatic drop attacks and syncope (69). Head-up tilt testing can establish this by demonstrating orthostatic hypotension that reproduces symptoms. Resolution of symptoms with treatment of the orthostatic hypotension confirms the diagnosis.

In some patients, drop attacks may represent a form of functional neurologic disorder, and such individuals may have additional precipitating factors identified, including situational triggers, high levels of stress, and dissociation (56).

Diagnostic workup

	• A thorough history and examination are appropriate in patients with presumed drop attacks, with careful attention in the history to any warning or aura, precipitating factors (including emotional stimuli), loss of consciousness, or ictal manifestations.
	• Evaluation should include assessment or orthostatic pulse and blood pressure (ie, supine, standing, and standing after 3 minutes).
	• Depending on the clinical circumstances, various diagnostic studies may be necessary.

A thorough history and examination are appropriate in patients with presumed drop attacks, with careful attention in the history to any warning or aura, precipitating factors (including emotional stimuli), loss of consciousness, or ictal manifestations. Observations from witnesses can be particularly helpful in clarifying the features of the episodes and in focusing the differential diagnosis. Prior cardiovascular disease, palpitations, strokes or transient ischemic attacks, movement disorders (including Parkinson disease, progressive supranuclear palsy, myoclonus, ataxia, and asterixis), presyncope or syncope, headaches, amaurosis, aural fullness, hearing loss, tinnitus, vertigo, cervical spondyloarthropathy, and any severe orthopedic problems or peripheral vascular disease involving the legs should be noted. Medications should be thoroughly reviewed, with particular attention to agents that may precipitate seizures, orthostatic hypotension, or sedation. Examination should identify any signs of raised intracranial pressure (including papilledema), evidence of previous strokes, movement disorders affecting postural tone or producing abnormal movements of the legs or trunk, myelopathy, ataxia, postural instability, leg weakness or spasticity, severe sensory loss in the legs, or mechanical/orthopedic leg dysfunction.

Evaluation should include assessment or orthostatic pulse and blood pressure (ie, supine, standing, and standing after 3 minutes). Depending on the clinical circumstances, various diagnostic studies may be necessary, including electrocardiography, Holter monitoring, cervical spine imaging, brain imaging, vascular imaging (eg, Doppler ultrasonography, magnetic resonance angiography, CT angiography, or traditional angiography), electroencephalography, audiograms, electronystagmography or video nystagmography, and vestibular evoked myogenic potential testing.

Management

	• With a varied constellation of causes, no single therapy is appropriate for all drop attacks.
	• Therapy is instead directed at treatment of the underlying cause.
	• Treatment is not generally indicated for individuals with an isolated drop attack and unrevealing medical and neurologic evaluations.
	• In patients with repeated falls, steps should be taken to minimize the risk of injury.
	• Older adults, particularly those with falls, should undergo assessment of bone mineral density by dual-energy x-ray absorptiometry (DEXA) of the distal forearm, lumbar spine, and proximal femur.

With a varied constellation of causes, no single therapy is appropriate for all drop attacks. Therapy is instead directed at treatment of the underlying cause. Treatment is not generally indicated for individuals with an isolated drop attack and unrevealing medical and neurologic evaluations (37).

Some authorities advocate conservative management of otolithic crises, particularly given that many cases have a flurry of episodes followed by remission (24; 02). A retrospective study found that intratympanic steroids were effective for treatment of such otolithic crises; if confirmed, this promises to be a first-line conservative treatment for drop attacks associated with Ménière disease and delayed endolymphatic hydrops, particularly as this approach has no inner-ear toxicity (31). However, otolithic crises can be associated with significant injuries and for some patients the attacks are so dangerous or intractable that chemical labyrinthectomy or surgery is indicated (02; 29). Otolithic crises have been treated successfully with either trans-tympanic gentamicin therapy or surgical ablation (labyrinthectomy) in the absence of serviceable hearing, or middle fossa vestibular nerve section to preserve serviceable hearing (03; 43; 23; 68; 29). Intratympanic gentamicin treatment appears to be a long-lasting and effective treatment for vestibular drop attacks in patients with Ménière disease (68; 70). Even older patients can be successfully treated with ablative surgery with excellent compensation and no vertigo or falls up to 10 years after surgery (23). Vestibular nerve section is usually recommended only for patients who have had symptoms for at least 5 years, unless the patient is severely incapacitated or is in danger of severe bodily harm because of otolithic crises (03).

In a small series of 10 patients, surgical decompression of Chiari I malformation had a high success rate (70%) for clinical improvement in patients with drop attacks (62). Tilt table testing had poor predictive value in judging the clinical response to surgical decompression and was useful in guiding surgical decision-making.

A cardiac pacemaker has been anecdotally reported to resolve drop attacks associated with ictal asystole in a patient with partial complex seizures (72).

Miglustat, a reversible inhibitor of the enzyme glucosylceramide synthase, has been anecdotally reported to resolve secondary cataplexy after 6 months of use in a patient with Niemann-Pick disease type C (71).

In patients with repeated falls, steps should be taken to minimize the risk of injury. Clinicians should discuss and address modifiable risk factors for fractures (as appropriate to the clinical situation):

• Excess alcohol intake (more than two drinks a day) • Cigarette smoking • Frail body habitus (weight less than 127 pounds or body mass index less than 20) • Inadequate diet • Estrogen deficiency • Impaired eyesight • Medications that facilitate development of osteomalacia (eg, phenytoin) • Unsafe footwear (heels more than a quarter inch; loose heels; strap sandals; smooth, hard soles; etc.) • Sedentary lifestyle • Home safety concerns (loose rugs, uneven surfaces, inadequate grab rails in the bathtub, etc.)

Older adults, particularly those with falls, should undergo assessment of bone mineral density by dual-energy x-ray absorptiometry (DEXA) of the distal forearm, lumbar spine, and proximal femur. Screening DEXA scans of the heels can also be informative, but the results of heel DEXA studies do not correlate perfectly with DEXA studies of the areas most likely to be fractured with falls (ie, the wrist and femoral neck). According to World Health Organization criteria, T-scores above -1 are normal, T-scores between -1 and -2.5 indicate osteopenia and a moderately increased risk of fracture, and T-scores below -2.5 are indicative of osteoporosis (or severe osteomalacia) and a severely increased risk of fracture. Significantly abnormal values (ie, generally T-scores less than -1.5 in the presence of other risk factors for osteoporosis or falls with injury, or less than -2.0 in the absence of other risk factors) should generally be managed with calcium and vitamin D supplementation, and bisphosphonate therapy (eg, alendronate).