Vestibular Paroxysmia

Clinical Aspects

If patients complain of short, repeated, paroxysmal attacks of vertigo lasting for seconds to minutes, which can sometimes be provoked by particular head positions, a vestibular paroxysmia is suspected. Spontaneous nystagmus is observed during the attack [26]. Other possible symptoms include unilateral tinnitus, hyperacusis, or facial contractions. Clinical examination in the attackfree intervals may in some patients reveal slight signs of permanent vestibular deficit, hypoacusis, or facial paresis on the affected side [26, 27].

Etiology

High-resolution MR imaging may show the compression of the 8th nerve by an artery (most often AICA) or more rarely by a vein in the region of the root entry zone of the vestibular nerve. However, such a result does not prove the diagnosis of paroxysmia, since such contacts can also be found in healthy subjects. The proposed mechanism is similar to that of nerve-blood vessel contact in trigeminal neuralgia.

Treatment

As in other neurovascular compression syndromes, an anticonvulsant (carbamazepine, slow-release formulation, 2 200 to 2 800 mg p.o. daily; phenytoin 1 250 to 1 400 mg p.o. daily; lamotrigine 100–400 mg p.o. daily) should be given initially [26, 27]. All drugs should be first administered in the lowest recommended dose and only gradually increased in order to prevent side effects. In general, a positive response to antiepileptic drugs can be achieved with low dosages and after a few days. If the symptoms do not resolve, a surgical approach may be considered [28]. There are no satisfactory follow-up studies on any of these treatment options, and the diagnostic criteria have not yet been fully established.

Downbeat Nystagmus

Clinical Aspects

Downbeat nystagmus is a central nystagmus that occurs during fixation and increases on downward gaze, especially on lateral gaze [6, 29, 30]. The head position relative to the earth’s vertical may play a role in some patients [31]. Convergence may suppress or enhance the nystagmus or even change its nystagmus toward an upbeat nystagmus in certain patients. Most patients also have vestibulocerebellar ataxia. Lesions that cause downbeat nystagmus occur in the vestibular cerebellum bilaterally and rarely in the underlying medulla [6].

Etiology

The main pathophysiological mechanism of downbeat nystagmus is a central imbalance of the vertical VOR [28] in combination with an abnormality of the vertical-torsional gaze-holding mechanism – the ‘neural integrator for eye movements’ [32]. The neural integrator is a network consisting of the medial vestibular complex and its connection to the cerebellum. The most common cause of downbeat nystagmus is cerebellar degeneration (hereditary, sporadic, or paraneoplastic). Recently, a report was published on a patient with glutamic-acid decarboxylase antibodies and a downbeat nystagmus in addition to signs of a stiff person syndrome [33]. Other important causes are Arnold-Chiari malformation and drug intoxication (especially anticonvulsants and lithium). In everyday practice, cerebellar atrophy, Arnold-Chiari malformation, various cerebellar lesions (multiple sclerosis, vascular, tumors), and idiopathic causes account for approximately one fourth each of cases of downbeat nystagmus [30, 34].

Treatment

Since a loss of inhibitory cerebellar influence on the vestibular nuclei is one of the main pathophysiological mechanisms of downbeat nystagmus, it seems expedient to investigate substances that may help re-establish such cerebellar influence on the brainstem. The vestibulocerebellar efferences to the vestibular nuclei are gabaergic; thus, most drugs investigated were GABA-A agonists. The GABA-A agonist clonazepam (2 1 mg daily) was recently reported to have a positive effect on so-called idiopathic downbeat nystagmus (e.g. no pathological findings on MRI) [35]. This supports older observations that clonazepam (0.5 mg p.o. three times daily) and the GABA-B agonist baclofen (10 mg p.o. three times daily) [36, 37] reduce the velocity in downbeat nystagmus. Gabapentin (an alpha- 2-delta calcium channel antagonist) [38] might also have weak positive effects and reduces in some patients downbeat nystagmus. A placebo-controlled, doubleblind study with a crossover design investigated the effect of the potassium channel blocker 3,4-diaminopyridine in 17 patients with downbeat nystagmus [39]. Potassium channel blockers can increase the spontaneous firing rate of the cerebellar Purkinje cells and therefore the inhibitory effect on the vestibular nuclei. On average, the potassium channel blocker reduced the slow-phase velocity of the nystagmus by more than 50% [39]. The same group reported a similar effect of 4- aminopyridine (10 mg orally) in a single patient [40]. This substance penetrates the blood-brain barrier better than 3,4-diaminopyridine and may therefore be more effective. The potassium channel blockers also seem to have a specific influence on the gravity-dependent component of the vertical velocity bias of downbeat nystagmus [41]. This might explain why patients who do not show such a vertical velocity bias and have more offset in the null position (e.g. the position at which the nystagmus velocity is minimal) do not seem to benefit in the same