Cerebellar dizziness and vertigo: etiology, diagnostic evaluation, and treatment

Dizziness and vertigo are common symptoms
in the general population.
The most common causes are peripheral or central vestibular or ocular dyskinesia, functional impairment, or rare nonvestibular disorders
.
The central cause of dizziness or vertigo is primarily dysfunction of brainstem-cerebellar vestibular, eye-movement, or sensorimotor pathways
.
Specifically, cerebellar dizziness and vertigo are an umbrella term for a group of disorders that present symptoms
of cerebellar dysfunction during clinical examination of eye movement, vestibular, or postural systems.
The timing of symptom onset is heterogeneous and can be divided into three types: (1) persistent manifestations (e.
g.
, degenerative cerebellar disease); (2) recurrent episodes of dizziness and vertigo (eg, vestibular migraine, episodic ataxia) or (3) acute vertigo or vertigo episodes (e.
g.
, stroke or inflammation).

The incidence of cerebellar dizziness and vertigo is often underestimated due to inaccurate examination of central eye movements and vestibular system
.
Chronic cerebellar dizziness and vertigo are the cause
of approximately 10% of all patients presenting to a tertiary dizziness/vertigo center.
Depending on the etiology, the average time to diagnose chronic disease is 5-10 years
.
The most common recurrent vestibular syndrome, such as vestibular migraine, can also present clinically with cerebellar symptoms
.
Among acute dizziness and vertigo symptoms, cerebellar lesions account for about two-thirds of central lesions and about 2.
5%-6.
5%
of all acute cases.
In this article, we will describe the most common causes, clinical signs, and symptoms in patients with chronic, recurrent, and acute cerebellar dizziness and vertigo, as well as helpful diagnoses to support diagnostic and treatment strategies
in affected patients.

Causes of cerebellar dizziness/vertigo

Chronic course

In patients with chronic cerebellar dizziness and vertigo, the most common causes are as follows: (1) degenerative form (70% of cases), including idiopathic tardive cerebellar ataxia, multiple system atrophy with obvious cerebellar features (MSA-c), idiopathic jerky nystagmus syndrome (DBN), cerebellar ataxia syndrome (CANVAS) with neuropathy and vestibular reflex loss, orthostatic tremor or many other rare diseases (►Table 1); (2) hereditary form (10% of cases), mainly due to spinal cerebellar ataxia or episodic ataxia; (3) Acquired form (20% of cases), mainly due to autoimmune/paraneoplastic syndrome (such as related to anti-GAD antibodies), poisoning (such as alcohol, antiepileptic drugs, lithium), infection (such as varicella-zoster induced cerebellitis), or vitamin deficiency (such as vitamin B12).

In some cases, the exact cause of chronic cerebellar dizziness and vertigo cannot be elucidated or can only be diagnosed
dynamically based on signs and symptoms during follow-up.

Table 1 Causes of cerebellar dizziness and vertigo

Episodic course

In patients diagnosed with cerebellar dizziness and vertigo, about 30% have a recurrent course
.
The duration of seizures varies from seconds to hours, rarely to days, and frequency from
several times a day to once a month.
Episodes may occur alone or as an acute exacerbation
of chronic symptoms such as dizziness or vertigo.
The most important differential diagnosis of episodic cerebellar dizziness/vertigo is vestibular migraine and episodic ataxia
.
Although the pathophysiology of vestibular migraine is not limited to the cerebellum, there is several evidence that cerebellar involvement occurs during and between attacks: in acute vestibular migraine, central positional vertigo or nystagmus are common features, suggesting vestibular cerebellar involvement
.
In addition, patients with vestibular migraine show mild cerebellor-ocular motor dysfunction in the seizure-free period, which tends to
increase with the duration of the disease.
Episodic ataxia is a group of clinically heterogeneous disorders with eight known subtypes
based on clinical and genetic characteristics.
Episodic ataxia type 2 (EA2) is the most common subtype
.
In approximately 60% of patients, mutations
in the CACNA1A gene encoding P/Q type calcium channel α-subspecies were identified.

Acute course

Dizziness and vertigo are the most common complaints
of posterior circulation stroke.
Most lesions with isolated vestibular symptoms without other neurological damage involve the cerebellum
.
The vascular region of the posterior inferior cerebellar artery is the most common, followed by the superior cerebellar artery and the anterior inferior cerebellar artery (AICA).

Because the labyrinth artery is also involved, AICA infarction often results in both peripheral and central vestibular and auditory symptoms
.
Cerebellar lesions confined to lobules, nodules, tonsils, epivermis, and cerebellar feet present with isolated vertigo and imbalance
.
In multiple sclerosis, the cerebellum foot is often affected
by inflammatory damage.

Diagnostic methods of cerebellar dizziness and vertigo

medical history

Patients with suspected cerebellar dizziness or vertigo should be evaluated
by questions about symptoms, onset and duration of symptoms, precipitating factors, and accompanying symptoms.

During the chronic course, approximately 80% of patients describe persistent dizziness and vertigo (mostly exercise-dependent), postural imbalance in 77%, dizziness in 16%, and rotational vertigo
in 2%.
In about 30% of cases, patients may experience episodes of dizziness or vertigo caused by postural changes
.
Factors that further exacerbate symptoms were reported to be dark environments (30%), activity on uneven ground (20%), emotional stress (10%), in some cases (5%), and alcohol consumption (5%)
.
The most common concomitant symptoms were gait disturbance (70%), falls (40%), tremor (22%), abnormal fine motor control (20%), dysarthria (20%), diplopia (18%), anxiety (19%), blurred vision (17%), nausea or vomiting (10-15%), urinary incontinence (5%), erectile dysfunction (1%), or repeated sweating (0.
5%)
.

In patients with recurrent cerebellar dizziness or vertigo, that is, due to vestibular migraine or episodic ataxia, symptoms are described in most cases as vertigo, followed by dizziness or imbalance
.
The duration of symptoms of vestibular migraine is 5 minutes to 72 hours (according to Barany Association criteria), seconds to minutes for type 1 episodic ataxia and hours
for type 2 episodic homopathy.
Predisposing factors such as exercise, emotional stress, or alcohol often predispose to type 2 episodic ataxia
.
Vestibular migraine is accompanied by migraine features (at least two migraine features, photophobia/phobia, visual aura)
in at least 50% of episodes.
Patients with episodic ataxia may describe dysarthria, diplopia, muscle weakness, and headache as common symptoms
during episodic episodes.

About 50% to 60% of patients with acute cerebellar syndrome experience dizziness and 40% to 50% develop vertigo
.
The duration of symptoms varies from a few minutes (transient ischemic attack) to a few weeks (large cerebellar lesions
).
Acute cerebellar lesions (caused by stroke or inflammation) are usually unprecipitating, which is an adjunct to differentiate from peripheral vestibular disorders such as BPPV
.
The most common concomitant features of acute cerebellar disease are hemiplegia, tendency to fall, gait instability, and diplopia
.

Signs of eye movement

Because ocular motor dysfunction can be the single clinical sign of cerebellar dizziness/vertigo, a thorough examination of eye movement control is the most important key
to the diagnosis of cerebellar dizziness and vertigo.
Clinical examination should include nystagmus (fixed or positional nystagmus, spontaneous or provoked nystagmus), smooth tracking, gaze, saccade, vestibular reflex (VOR), fixed vision suppression with VOR, eye alignment, and vestibular asymmetry (subjective visual verticality (SVV) by assessing acute vestibular syndrome
).
。 Typical cerebellar eye movement disorders include saccade smooth tracking, gaze-induced nystagmus, VOR gaze inhibition disorder, reverse skew, DBN, rebound nystagmus, central positional nystagmus, periodic alternating nystagmus, dislocation shaky nystagmus, medial/exotropia, or SVV deviation (acute phase) (►Figure 1, ►Table 2)

Fig.
1 Anatomy
of cerebellar eye motor control.
The most important cerebellar regions in eye motor control are the pom-pom lobule, nodules, vermis, and parietal nucleus
.
Focal lesions can cause characteristic ocular movement signs, which are listed
in each area.

Table 2 Cerebellar dizziness and vertigo: chronic, recurrent, and acutely manifested ocular motor signs

Signs of eye movement during the course of chronic attacks

Patients with chronic cerebellar dizziness and vertigo exhibit multiple ocular motor dysfunctions
.
Thus, ocular movement examination is very sensitive to support the diagnosis, but in most cases specificity is not sufficient to differentiate the cause.

The most common ocular movement sign in patients with chronic cerebellar dizziness and vertigo was abnormal scanning smoothing in all directions in 85% of patients, with only 7% in vertical and 3%
horizontally.
Abnormal scanning smooth tracking occurs in 95% of patients with degenerative cerebellar disorder, 88% of patients with hereditary cerebellar disorder, and 90% of patients with acquired cerebellar disorder
.

80% of patients with chronic cerebellar dizziness and vertigo often have gaze disturbance
.
Horizontal gaze-induced nystagmus is more common
in degenerative (55%) than genetic (42%) and acquired (33%).
Rebound nystagmus occurred in 23% of patients and shaky nystagmus occurred in 57% of patients (~40% vertically, ~22% horizontally).

Central fixed vision nystagmus occurs in approximately 25% of cases (most commonly degenerative and acquired), with DBN being the most common (two-thirds of cases).

Saccade impairment is also common (34%) and mostly has a similar degree of impact
on the measurement of vertical and horizontal saccades.

Fascination may be hypersaccade (involving the parietal nucleus of the cerebellum) or contraction saccade (involving the cerebellar vermis).

Abnormal conjugated eye movements were observed in 29% of patients, dislocation in hyperopia in 50%, and dislocation
in myopia in 84% of patients.

Fixed visual inhibition of VOR is impaired in 64% of patients, mainly in both horizontal and vertical directions
.
The cephalic pulse test may be pathologically in up to half of patients with cerebellar dizziness (degeneration> genetic >acquired
).
This can be explained by false-positive head pulse testing and delayed rebound saccades, partly due to cerebellar and peripheral vestibular disorders (e.
g.
, CANVAS).

Ocular recordings may be helpful in distinguishing between false-positive and true-positive head pulses
.
Asymmetric pathological clinical head pulse test is rarely detected in chronic cerebellar vertigo and vertigo (8% of cases).

Signs of eye movement in a recurrent course

In the most common recurrent forms of cerebellar dizziness and vertigo, vestibular migraine and episodic ataxia present with oculomotor signs
to varying degrees.
In patients with episodic ataxia, particularly type 2, severe cerebellar motor signs (eg, DBN, gaze-induced nystagmus) are almost intense
.
Most patients also present with severe central nystagmus patterns such as DBN or rebound nystagmus during attacks
.
Patients with vestibular migraine present with mild oculomotor dysfunction
in about 15% to 40% of cases.
The most common on clinical examination are central positional nystagmus (12-28%), shaky head concussion (2-15%), gaze-induced nystagmus, and saccade smooth tracking
.
Ocular motor dysfunction tends to
worsen during the course of the disease.

Signs of eye movement during the course of acute presentation

Acute cerebellar lesions with dizziness or vertigo often involve the vestibular cerebellum (pompom lobules, parapom-pom lobules, tonsils, and tubercles), cerebellar vermis, parietal nucleus, or structures
of the lower cerebellar feet.
Thus, depending on the site of the lesion, ocular movement examination reflects typical fixation, smooth tracing, or saccade abnormalities
.
Acute cerebellar syndrome can be divided into four archetypes, which may occur incompletely or concurrently:

Other neurological symptoms

On neurological examination in patients with cerebellar dizziness and vertigo, the most common findings are problems with coordination and fine motor.

About half of patients with chronic cerebellar dysfunction have ranging impairment on finger-to-finger testing, and one-third show incoordination
with the knee-tibial test.
One-third of patients have dyskinesia, and about 15% have intentional tremor and fine motor impairment
.
Patients occasionally have dysarthria (20%) and imbalance (17%, n=55).

The average score of SARA (as an overall assessment of cerebellar function) is about 15 points (higher score for acquired forms [29 points], lower scores for degenerative and heritable).

About 30% of patients have other neurological signs
of polyneuropathy.
Falls (50% are recurrent) occur frequently in patients with chronic cerebellar vertigo and vertigo
.
The consequences of falls are often more severe
.
In people with cerebellar syndrome, more than 30% of fall injuries result in a doctor's
attention.
The odds of falls were about 16 times
higher than in age-matched healthy controls.

Laboratory tests for posture and gait

Quantitative pose tracing can show patterns consistent with chronic cerebellar vertigo and vertigo, but these studies are not suitable for making a definitive diagnosis
.

In postural tractography, patients with cerebellar vertigo and vertigo have increased
body swing paths in all directions and under all conditions (with or without polysensory interference).
In the spectral Fourier analysis, about 15% of patients experienced a typical 3 Hz cerebellar rock.

In the rare subset of patients with orthostatic tremor, a cerebellar phenotype may appear on ocular motor examination, with a highly characteristic peak in frequency between 14 and 18 Hz that can be used to confirm the diagnosis
.
Artificial network-based pose map analysis has high sensitivity and specificity
in defining patients with cerebellar dizziness and vertigo.

Patients with cerebellar syndrome exhibit typical pathological gait patterns, including wider distance between feet, shorter step lengths, and high temporal and spatial variability
in gait patterns.
In addition to clinical examination of gait, visual gait assessment can help document these typical changes in gait and predict the likelihood of
falls.
To fully assess cerebellar gait and distinguish it from other forms of ataxia gait, several gait conditions
should be examined.
Having patients walk in conditions that challenge their biomechanical, sensory, or cognitive resources can help better describe the cause of
their gait disorder.
In general, patients with cerebellar ataxia have higher levels of gait variability than vestibular gait ataxia
.
In cerebellar syndrome, gait variability increases with both slow and brisk walking, while vestibular ataxia increases
only with slow walking.
Characteristic patterns of gait variability in cerebellar patients suggest disturbance of sensory feedback integration (when walking slowly) and cerebellar vibration dysfunction and multiarticular motor feedforward coordination (mainly during rapid walking).

Cerebellar pathologies that primarily affect cerebellar pom-pom lobules (e.
g.
, DBN) exhibit more pronounced gait variability when walking slowly and briskly, which highlights the importance of the vestibular cerebellum for sensory feedback, primarily when walking slowly (►Figure 2).

Gait variability can serve as an alternative marker
for tracking a patient's clinical course or measuring the success of a therapeutic intervention.
The quantification of gait variability has further significance for the prediction of falls in patients with cerebellar syndrome
.
A recent study showed that high gait variability, especially when walking slowly, was significantly associated
with the risk of falls in patients with degenerative, hereditary, and sporadic cerebellar disorders.

Fig.
2 Gait analysis and gait control
of cerebellar ataxia.
Compared with healthy subjects (HS, middle), patients with cerebellar ataxia (CA, left) have increased
gait variability during slow and brisk walking.
Variability in slow walking is determined by sensory integration, which is mainly mediated by the vestibular cerebellum and cerebellar vibration when walking quickly, located in the vermis (right).

Imaging and genetics

Every patient newly diagnosed with cerebellar dizziness or vertigo should undergo standardized diagnostic tests, including imaging, laboratory tests, and, in some cases, genetic testing
.
As the preferred imaging modality for acute cases, computed tomography (CT) and CT angiography
should be performed at a minimum.
Magnetic resonance (MR) diffusion diffusion and perfusion-weighted imaging can increase diagnostic accuracy
.
For recurrent and chronic cerebellar dizziness and vertigo, MRI should be performed to rule out cerebellar injury, atrophy, or other structural changes
.
If a degenerative form of cerebellar syndrome is suspected, [18F]FDG-PET
may be performed.
Cerebrospinal fluid analysis
is performed if underlying paraneoplasm, autoimmune, or infectious causes of cerebellar dysfunction need to be excluded or confirmed.
If phenotype and family history point to an underlying genetic form of cerebellar syndrome, genetic analysis
may be considered.
Gene selection may work with human geneticists to adapt phenotype
.

treat

Treatment of patients with cerebellar dizziness/vertigo must be multimodal and requires rehabilitation exercises including eye stabilization, posture, gait control, occupational therapy of limb function, and medication.

drug therapy

Aminopyridine, clozoxadone, and N-acetyl-DL-leucine have good efficacy
in patients with cerebellar dizziness and ocular dyskinesia.

Aminopyridine has therapeutic effects
on all forms of cerebellar dizziness and vertigo.
In patients with DBN, 3,4-diaminopyridine, 4-aminopyridine (4-AP), and fampridine extended-release agents (also known as davapyridine or aminopyridine) have all shown significant reductions
in nystagmus intensity in several randomized controlled trials.
4-AP can reduce DBN symptoms, especially in patients with cerebellar atrophy; Halve the slow phase speed of the DBN; And at doses of 5-10 mg four times a day, it can improve vision and motor performance
.
A dose of 10-20 mg per day of fampridine is effective in reducing the intensity of DBN (►Figure 3).

As confirmed in a single case report, 4-AP can also be used in patients
with central positional nystagmus.
4-AP and fampridine have been identified as treatment options for EA2 patients: they can effectively reduce the number of seizures in EA2 patients and improve the quality of life of
patients.
Flupyridine is also effective in reducing EA2 episodes and may be similar to acetazolamide, but with fewer
side effects.
4-AP also reduces gait variability and fall frequency
in patients with degenerative and acquired cerebellar syndrome.

Fig.
3 Effect
of fampridine on downward jumping nystagmus.
(A) Raw recordings
of vertical eye position at baseline, 180 min for first dose, 2 weeks for dosing, and 4 weeks for elution in DBN patients.
(B) Average slow phase velocity (SPV)
at baseline, 180 minutes of first dose, 2 weeks of dosing, and 4 weeks of elution in 10 DBN patients.
SPV after administration is significantly lower than baseline or after
the elution phase.

Cloxazone is an activator of calcium-activated potassium channels, and in a single uncontrolled study, it was demonstrated that clozoxazone 500 mg three times daily improved postural stability
in patients with DBN.

N-acetyl-DL-leucine has been used in France since 1957 for the treatment of dizziness and vertigo, and in an observational study of patients with cerebellar ataxia of different etiologies, a dose of 5 g per day of N-acetyl-DL-anine significantly improved
disorder scores (i.
e.
, SARA and SCAFI), gait changes, and quality of life.
Similar effects
are found for neurometabolic disorders associated with cerebellar dysfunction (e.
g.
, Niemann-Pick disease type C).

Rehabilitation

The effect of rehabilitation on cerebellar dizziness and vertigo has not been specifically evaluated
in controlled trials.
However, there is indirect evidence that physiotherapy may be effective for
these conditions.

A meta-analysis of interventional rehabilitation studies of approximately 300 patients with hereditary cerebellar ataxia showed statistically significant improvements
in at least one outcome measure of ataxia, gait, or balance, including coordination and balance training, cycling regime, biofeedback balance training, respiratory muscle training, and treadmill training.
Although interventions were heterogeneous, multimodal rehabilitation programmes incorporating elements of balance training, inpatient rehabilitation, and occupational therapy were likely to be most effective
.
These interventions may improve function, mobility, ataxia, and balance
in degenerative cerebellar syndrome.
These data are consistent with the effects of multimodal vestibular rehabilitation in patients with peripheral vestibular disorder who have shown convincing effects
in mobility, fall prevention, and quality of life.

conclusion

Cerebellar dizziness and vertigo are clinically important, accounting for approximately 10% of all patients presenting to tertiary dizziness centers, but have been underestimated
to date.
Patients are severely
affected in their daily lives.
Falls and mobility problems are more common
.
Symptoms are diverse and include persistent, recurrent, and acute forms, with the main complaints being dizziness, vertigo, postural imbalance, or vibratory hallucinations
.
A thorough examination of the central eye movement and vestibular system by an experienced neurologist is key to correct diagnosis and is therefore essential
.
The most common signs are smooth saccade tracking, gaze-induced nystagmus, shaky head nystagmus, misalignment of the eye in hyperopia and nearsightedness, disturbance of VOR gaze inhibition, impaired saccade of saccade indicators, and central gaze nystagmus (mostly DBN).

Apparent assessment of posture and gait is helpful in diagnosis
.
In postural tractography, 15% of patients can detect typical cerebellar 3-Hz wiggling
.
Pose profiling data based on artificial networks has high sensitivity and specificity
in distinguishing cerebellar dizziness and vertigo from other balance disorders.
Gait analysis shows increased gait variability during slow and brisk walking and can be used to predict an individual's risk
of falling.
Finally, patients with cerebellar dizziness and vertigo should be treated with a multimodal approach that includes balanced rehabilitation and pharmacotherapy (depending on symptoms).

Aminopyridine has been shown to be effective
in patients with cerebellar gait disorder, DBN, and EA2.
N-acetyl-DL-leucine may be an alternative option for patients with cerebellar ataxia, i.
e.
, if caused
by a neurometabolic disorder.
Further controlled trials are needed to confirm the effects of
these drugs in larger populations.