Published online: 30.12.

2019

Cerebellar Dizziness and Vertigo: Etiologies,

Diagnostic Assessment, and Treatment
Andreas Zwergal, MD1,2 Katharina Feil, MD1,2 Roman Schniepp, MD1,2 Michael Strupp, MD1,2

1 Department of Neurology, University Hospital, Ludwig Maximilians Address for correspondence Andreas Zwergal, MD, Department of
University Munich, Munich, Germany Neurology and German Center for Vertigo and Balance Disorders,
2 German Center for Vertigo and Balance Disorders, Ludwig Ludwig Maximilians University Munich, Marchioninistrasse 15,
Maximilians University Munich, Munich, Germany D-81377 Munich, Germany
(e-mail: [email protected]).
Semin Neurol

Abstract Cerebellar dizziness and vertigo account for approximately 10% of diagnoses in a
tertiary dizziness center. This term summarizes a large group of disorders with chronic
(degenerative, hereditary, acquired cerebellar ataxias), recurrent (episodic ataxias), or
acute (stroke, inflammation) presentations. Key to the diagnosis is a comprehensive

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examination of central ocular motor and vestibular function. Patients with cerebellar
dizziness and vertigo usually show a pattern of deficits in smooth pursuit, gaze-holding,
saccade accuracy, or fixation-suppression of the vestibulo-ocular reflex. Central fixation
nystagmus (e.g., downbeat nystagmus), gaze-evoked nystagmus, central positional
nystagmus, or head-shaking nystagmus with cross-coupling (i.e., horizontal head
Keywords shaking causing inappropriate vertical nystagmus) occurs frequently. Overlap syn-
► cerebellar disorders dromes with peripheral vestibular disorders, such as cerebellar ataxia, neuropathy, and
► downbeat nystagmus vestibular areflexia, exist rarely. Posturography and gait analysis can contribute to
► ocular motor diagnostic differentiation, estimation of the risk of falls, as well as quantification of
disorders progression and treatment effects. Patients with cerebellar dizziness and vertigo
► aminopyridines should receive multimodal treatment, including balance training, occupational thera-
► acetyl-leucine py, and medication.

Dizziness and vertigo are frequent symptoms in the general The frequency of cerebellar dizziness and vertigo tends to be
population.1 The most common causes are peripheral or underestimated, which is often due to an inaccurate examina-
central vestibular or ocular motor disorders, functional dis- tion of central ocular motor and vestibular systems.7 Chronic
orders, or rarely nonvestibular disorders.2 Central etiologies cerebellar dizziness and vertigo is the cause for approximately
of dizziness or vertigo mostly originate from dysfunction of 10% of all patients who present to a tertiary dizziness center.5
brainstem-cerebellar vestibular, ocular motor, or sensorimo- Mean time to diagnosis in chronic disorders is 5 to 10 years,
tor circuits. Specifically, cerebellar dizziness and vertigo is a depending on the etiology. The most frequent recurrent
general term for a group of disorders which all share signs of vestibular syndrome, vestibular migraine, can also clinically
cerebellar dysfunction on clinical examination of ocular manifest as a cerebellar phenotype.8 In acute dizziness and
motor, vestibular, or postural systems.3–5 The time course vertigo presentations, cerebellar lesions account for about
of presentations is heterogeneous and can be classified into two-thirds of central lesions, or approximately 2.5 to 6.5% of
three types: (1) persistent presentations (e.g., in degenera- all acute cases.9,10 In this article, we will describe the most
tive cerebellar disorders); (2) recurrent episodes of dizziness common etiologies, clinical signs, and symptoms of patients
and vertigo (e.g., in vestibular migraine, episodic ataxias); or with chronic, recurrent, and acute cerebellar dizziness and
(3) acute onset of dizziness or vertigo (e.g., in stroke or vertigo, together with helpful diagnostic tests to support the
inflammation).4–6 diagnosis and therapeutic strategies in affected patients.

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Cerebellar Dizziness and Vertigo Zwergal et al.

due to autoimmune/paraneoplastic syndromes (e.g., associated

Etiologies of Cerebellar Dizziness and
with anti-GAD antibodies), exposure to toxins (e.g., alcohol,
Vertigo
antiepileptics, lithium), infections (e.g., varicella zoster-induced
Chronic Presentations cerebellitis), or vitamin deficiency (e.g., vitamin B12).20 In some
In patients with chronic presentations of cerebellar dizziness cases, the exact origin of chronic cerebellar dizziness and vertigo
and vertigo, the most frequent etiologies are the following: (1) cannot be elucidated or can be diagnosed only on the basis of the
degenerative forms (70% of cases), including idiopathic dynamics of signs and symptoms during follow-up.
late-onset cerebellar ataxia, multiple system atrophy with
prominent cerebellar features (MSA-c), idiopathic downbeat Recurrent Presentations
nystagmus syndrome (DBN), cerebellar ataxia with neuropathy Recurrent attacks are reported in approximately 30% of
and vestibular areflexia syndrome (CANVAS), orthostatic trem- patients with the diagnosis of cerebellar dizziness and vertigo.
or and many others (►Table 1)11–18; (2) hereditary forms (10% The duration of attacks varies from seconds to hours and,
of cases), mostly due to spinocerebellar ataxias or episodic rarely, days, and the frequency varies from several times per
ataxias18,19; and (3) acquired forms (20% of cases), mostly day to once every month.5 Attacks may occur in isolation or as

Table 1 Etiologies of cerebellar dizziness and vertigo

Time course Etiologies

Chronic presentations of Degenerative

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cerebellar dizziness and
Idiopathic late-onset cerebellar ataxia
vertigo
Multiple-system atrophy of cerebellar type
Downbeat nystagmus syndrome
Cerebellar ataxia, neuropathy, vestibular areflexia syndrome
Orthostatic tremor
Rare other types
Hereditary
Spinocerebellar ataxias (most frequent subtypes 1, 2, 3, 6)
EAs (most frequent EA-1 and EA-2)
Niemann-Pick type C (cerebellar phenotype)
Rare other types
Acquired
Autoimmune
Non-paraneoplastic (e.g., anti-GAD ab, anti-TPO ab, anti-gliadin ab)
Paraneoplastic (onconeural ab, cell surface ab)
Toxic (alcohol, medications, chemical toxins, thermic cerebellar degeneration, metabolic disorders)
Vitamin deficiencies (vitamin B1, B12, E)
Infectious
Acute cerebellitis (herpesvirus, enterovirus, orthomyxovirus, parvovirus B19, gram-negative bacteria
[e.g., Brucella, Rickettsia, Borrelia], gram-positive bacteria [e.g., Tropheryma whippelii], mycoplasma)
Post-/parainfectious cerebellar syndrome
Chronic cerebellar infections
Recurrent presentations of EAs (type 1–8, most frequent EA-1 and EA-2)
cerebellar dizziness and
Vestibular migraine
vertigo
Acute presentation of Acute cerebellar stroke (PICA > SCA > ICA)
cerebellar dizziness
Tonsillar lesions
and vertigo
Nodular lesions
Floccular lesions
Peduncular lesions
Vermis lesions
Acute inflammation (multiple sclerosis, sarcoidosis, vasculitis)

Abbreviations: EA, episodic ataxia; ICA, inferior cerebellar artery; PICA, posterior inferior cerebellar artery; SCA, superior cerebellar artery.
Source: Adapted from Feil et al,5 Kim et al,9 and Nachbauer et al.20

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 Cerebellar Dizziness and Vertigo Zwergal et al.

an add-on to chronic complaints of dizziness or vertigo. The In patients with recurrent presentations of cerebellar
most important differential diagnoses of recurrent pathologies dizziness or vertigo—namely, due to vestibular migraine or
with cerebellar presentations are vestibular migraine and episodic ataxias—symptom quality is described as vertigo in
episodic ataxias.19,21 Although the pathophysiology of vestib- most cases, followed by dizziness or postural instabili-
ular migraine is not restricted to the cerebellum,22 several lines ty.19,22 Symptom duration is 5 minutes to 72 hours in
of evidence point to cerebellar involvement both during and vestibular migraine (according to Barany Society criteria),
between attacks: in acute vestibular migraine, central posi- seconds to minutes for episodic ataxia type 1, and hours for
tional vertigo or nystagmus are common features, which episodic ataxia type 2.19,21 Trigger factors like physical
suggest an involvement of the vestibulocerebellum.23 Further- exertion, emotional stress, or alcohol frequently provoke
more, patients with vestibular migraine show subtle cerebellar attacks in episodic ataxia type 2.19,24,25 Accompanying
ocular motor dysfunction in the attack-free interval, which features for vestibular migraine are migraine features
tends to increase as a function of disease duration.8 Episodic (headache with at least two migraine characteristics, pho-
ataxias represent a clinically heterogeneous group of disor- to-/phonophobia, visual aura) in at least 50% of attacks.
ders, with eight known subtypes according to clinical and Patients with episodic ataxias may report dysarthria, dip-
genetic characteristics.19 Episodic ataxia type 2 (EA2) is the lopia, muscle weakness, and headaches as co-symptoms
most common subtype. In approximately 60% of patients, during attacks.24,25
mutations of the CACNA1A gene, which encodes the α-subunit Patients with acute cerebellar syndromes report dizziness
of the P/Q-type calcium channel, are found.24,25 in approximately 50 to 60%, and vertigo in 40 to 50% of cases.
Symptom duration varies from minutes (in transient ische-

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Acute Presentations mic attacks) to weeks (in large cerebellar lesions).9 Acute
Dizziness and vertigo are the most common chief complaints in cerebellar lesions (due to stroke or inflammation) regularly
posterior circulation strokes.6,9 The majority of lesions with appear without a preceding trigger, which is a co-criterion
pure vestibular symptoms without other neurological deficits for differentiating from peripheral vestibular disorders (e.g.,
involve the cerebellum. The vascular territory of the posterior BPPV).28 Finally, the most common accompanying features in
inferior cerebellar artery is most frequently affected, followed acute cerebellar lesions are hemiataxia, falling tendency, gait
by the superior cerebellar artery and the anterior inferior instability, and double vision.
cerebellar artery (AICA).9,26 AICA infarcts often cause a mixed
peripheral and central vestibular and auditory phenotype, as Ocular Motor Signs
the labyrinthine artery is also involved.27 Cerebellar lesions A comprehensive examination of ocular motor control is the
confined to the flocculus, nodulus, tonsil, superior vermis, most important key to the diagnosis of cerebellar dizziness
and cerebellar peduncle manifest with isolated vertigo and and vertigo, as ocular motor dysfunction can occur as the
imbalance.9 The cerebellar peduncle is often affected by single clinical sign of this group of disorders.5,7 The clinical
inflammatory lesions in multiple sclerosis. examination should include tests for nystagmus (fixation or
positional nystagmus, spontaneous or provocation nystag-
mus), smooth pursuit, gaze-holding, saccades, vestibulo-
Diagnostic Approach to Cerebellar Dizziness
ocular reflex (VOR), fixation-suppression of the VOR, and
and Vertigo
ocular alignment and vestibular asymmetry (by assessment
History-Taking of the subjective visual vertical (SVV) in an acute vestibular
Patients with suspected cerebellar dizziness or vertigo syndrome).29 Typical cerebellar ocular motor disturbances
should be assessed by questions regarding the quality of are saccadic smooth pursuit, gaze-evoked nystagmus, im-
symptoms, onset and duration of symptoms, trigger factors, pairment of fixation suppression of the VOR, skew deviation,
and accompanying symptoms. DBN, rebound nystagmus, central positional nystagmus,
In chronic presentations, approximately 80% of patients periodic alternating nystagmus, perverted head-shaking
report persistent dizziness and vertigo (mostly motion nystagmus, eso-/exophoria, or deviation of the SVV (in acute
dependent), 77% postural imbalance, 16% light-headedness, lesions)5,30–34 (►Fig. 1, ►Table 2).
and 2% rotatory vertigo. Patients may have additional
attacks of dizziness or vertigo in approximately 30% of Ocular Motor Signs in Chronic Presentations
cases, mostly induced by changes in body position. Further Patients with chronic forms of cerebellar dizziness and
trigger factors reported to worsen symptoms are movement vertigo show a broad spectrum of ocular motor dysfunc-
in darkness (30%), on uneven ground (20%), during emo- tions.29 Therefore, the ocular motor examination is very
tional stress (10%), in certain situations (5%), and during sensitive to support the diagnosis, but in most cases not
consumption of alcohol (5%). The most frequently reported specific enough to distinguish the etiology.
accompanying symptoms are gait disturbances (70%), falls The following ocular motor signs are most frequent in
(40%), oscillopsia (22%), abnormal fine motor control (20%), patients with chronic cerebellar dizziness and vertigo: ab-
dysarthria (20%), double vision (18%), anxiety (19%), blurry normalities of saccadic smooth pursuit are found in 85% of
vision (17%), nausea or vomiting (10–15% of cases), urinary patients in all directions, 7% only in vertical direction, and 3%
incontinence (5%), erectile dysfunction (1%), or recurrent in horizontal direction. Saccadic smooth pursuit occurs in
attacks of sweating (0.5%).5 95% of patients with degenerative cerebellar disorders, 88%

Seminars in Neurology
Cerebellar Dizziness and Vertigo Zwergal et al.

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Fig. 1 Anatomy of cerebellar ocular motor control. The most important cerebellar regions for ocular motor control are the flocculus, nodulus,
vermis and fastigial nucleus. Focal lesions can cause characteristic ocular motor signs, which are listed for each region.

Table 2 Ocular motor signs in chronic, recurrent, and acute Table 2 (Continued)
presentations of cerebellar dizziness and vertigo
Type Clinical ocular motor signs
Type Clinical ocular motor signs Head-shaking nystagmus (60%)
Chronic Degenerative Square wave jerks (8%)
presentations
Saccadic smooth pursuit (88%) Saccadic dysmetria (30%)
of cerebellar
dizziness and Gaze-evoked nystagmus (83%) Pathological fixation suppression of VOR (42%)
vertigo
Primary position nystagmus (25%) Ocular misalignment in near gaze (73%)
Head-shaking nystagmus (60%) (False-) positive head-impulse test (27%)
Square wave jerks (13%) Recurrent Episodic ataxias, most frequent subtypes are EA 2 and
presentations EA 1
Saccadic dysmetria (30%)
of cerebellar
Acute stage
Pathological fixation suppression of VOR (52%) dizziness and
vertigo Central fixation nystagmus (80%)
Ocular misalignment in near gaze (86%)
Attack-free interval
(False-) positive head-impulse test (54%)
Saccadic smooth pursuit (90%)
Hereditary
Gaze-evoked nystagmus (90%)
Saccadic smooth pursuit (78%)
Central fixation nystagmus (mostly DBN)
Gaze-evoked nystagmus (78%)
(60%)
Primary position nystagmus (16%)
Vestibular migraine
Head-shaking nystagmus (40%)
Acute stage
Square wave jerks (38%)
Spontaneous nystagmus (45%)
Saccadic dysmetria (50%)
Central positional nystagmus (40%)
Pathological fixation suppression of VOR (54%)
Attack-free interval
Ocular misalignment in near gaze (84%)
Mild saccadic smooth pursuit (50%)
(False-)positive head impulse test (44%)
Mild central positional nystagmus (12–28%)
Acquired
Head-shaking nystagmus (2–15%)
Saccadic smooth pursuit (75%)
Acute presenta- Acute tonsillar lesions
Gaze-evoked nystagmus (69%) tions of cere-
Ipsilesional impairment of smooth pursuit
bellar dizziness
Primary position nystagmus (23%)
and vertigo Spontaneous nystagmus to the lesion side in
darkness

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 Cerebellar Dizziness and Vertigo Zwergal et al.

Table 2 (Continued) Ocular Motor Signs in Recurrent Presentations

In the most frequent recurrent forms of cerebellar dizziness
Type Clinical ocular motor signs and vertigo—vestibular migraine and episodic ataxias—ocu-
Contralesional SVV tilt lar motor signs are present to a variable extent. In patients
with episodic ataxias, especially subtype 2, severe cerebellar
Horizontal saccades, head-impulse test, caloric
response normal ocular motor signs (such as DBN, gaze-evoked nystagmus)
Acute nodular lesions are almost obligatory. Most patients also show severe central
Ipsilesional spontaneous horizontal nystagmus
nystagmus patterns during attacks, such as DBN or rebound
nystagmus.19,24 Patients with vestibular migraine show signs
Contraversive ocular tilt reaction
of mild ocular motor dysfunction in approximately 15 to 40%
Perverted head-shaking nystagmus
of cases. Central positional nystagmus (12–28%), head-shak-
Central positional nystagmus
ing nystagmus (2–15%), gaze-evoked nystagmus, and sac-
Impaired suppression of post-rotatory nystagmus cadic smooth pursuit are found most frequently in the
Acute peduncular lesions clinical examination. Ocular motor dysfunction tends to
Ipsilesional spontaneous nystagmus worsen during the course of the disease.8
Impaired ipsilesional smooth pursuit
Contralesional SVV tilt and ocular torsion Cerebellar Ocular Motor Signs in Acute Presentations
Saccades, head-impulse test, caloric response
Acute cerebellar lesions with the chief complaint of dizziness
or vertigo often involve structures of the vestibulocerebellum

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normal
Acute vermis lesions (flocculus, paraflocculus, tonsil, and nodulus), ocular motor
Hypometric saccades vermis, fastigial nucleus, or the inferior cerebellar peduncle.9
Central positional nystagmus
Accordingly, the ocular motor examination reflects typical
abnormalities of gaze-holding, smooth pursuit, or saccades,
Abbreviations: SVV, subjective visual vertical; VOR, vestibulo-ocular reflex. depending on the lesion site. Four prototypes of acute cerebel-
Source: Adapted from Feil et al5 and Kim et al.9
lar syndromes can be differentiated, which may also occur
incompletely or in combination:
Syndrome of a unilateral tonsillar lesion: Typical clinical
of patients with hereditary disorders, and 90% of patients signs of this rare syndrome may be an ipsilesional impairment
with acquired forms of cerebellar disorders. of smooth pursuit, a spontaneous nystagmus to the lesion side
Gaze-holding deficits are common in patients with chronic in darkness, and a small contralesional SVV tilt, while hori-
cerebellar dizziness and vertigo (80%). Horizontal gaze-evoked zontal saccades, head impulse test, and caloric response are
nystagmus is more frequent in degenerative forms (55%) than normal.38
in hereditary (42%) and acquired forms (33%). Rebound nys- Syndrome of a unilateral nodular lesion: Nodular lesions often
tagmus is found in 23% of patients, and head-shaking nystag- present with an ipsilesional spontaneous horizontal nystag-
mus in 57% of patients (vertical direction
40%, horizontal mus, contraversive ocular tilt reaction (SVV tilt, ocular torsion,
direction
22%). Central fixation nystagmus occurs in approx- and skew deviation), perverted head-shaking nystagmus (e.g.,
imately 25% of cases (most frequently in degenerative and DBN evoked by horizontal head-shake), positional nystagmus,
acquired forms), with DBN being the most common (two- and impaired suppression of post-rotatory nystagmus. Most of
thirds of all cases). Disturbances of saccades are also frequent these symptoms can be explained by a disinhibition of the
(34%), and mostly affect the metric of vertical and horizontal vestibular nucleus and velocity storage mechanism.39,40
saccades to a similar extent.5 Syndrome of a unilateral inferior cerebellar peduncle lesion:
Saccades may be hypermetric (involvement of the fastigial Patients may report isolated vertigo or postural imbalance
nucleus) or hypometric (involvement of the ocular motor because of gravity perception and control of postural vertical
vermis).35 Conjugate eye movement abnormalities are ob- dissociate in this syndrome. The most common clinical ocular
served in 29%, misalignments in distant view in 50%, and in motor signs are ipsilesional spontaneous nystagmus, impaired
near view in 84% of the patients.5,33 ipsilesional smooth pursuit, contralesional SVV tilt, and ocular
Impaired fixation suppression of the VOR occurs in 64% of torsion, as well as falling to the lesion side. Saccadic control,
all patients, mostly both in the horizontal and the vertical head impulse, and caloric testing are commonly normal.41
direction. The clinical head impulse test may be pathological Syndrome of a unilateral superior vermis lesion: Patients
in up to half of patients with cerebellar dizziness (degenera- with a lesion of the superior vermis often report prominent
tive > hereditary > acquired).5 This can be explained by a postural imbalance and dizziness. In the ocular motor exam-
false-positive head impulse test with delayed refixation ination, saccadic abnormalities such as hypometric saccades
saccades36 and partially by combined cerebellar and periph- can be detected. Some patients may show a central positional
eral vestibular disorders (e.g., in CANVAS).13,37 Oculographic nystagmus as the leading sign.35,42
recordings may help distinguish false-positive from true-
positive head impulses.36 An asymmetrically pathological Additional Neurological Signs
clinical head impulse test is found only rarely (8% of cases) The most common findings in the neurological examination
with chronic cerebellar dizziness and vertigo.5 of the patients with cerebellar dizziness and vertigo are

Seminars in Neurology
Cerebellar Dizziness and Vertigo Zwergal et al.

problems with coordination and fine motor skills. About half gait pattern.48 In addition to the clinical examination of gait,
of patients with chronic cerebellar dysfunction have dysme- apparative gait assessment can help document these typical gait
tria on the finger-to-finger test, and a third exhibit abnormal alterations and predict the likelihood of falls. For a comprehen-
heel-to-shin coordination. Dysdiadochokinesia is present in sive assessment of cerebellar gait and differentiation from other
one-third of patients, and intention tremor and fine motor forms of ataxic gait, several gait conditions should be tested.
disturbances in approximately 15% of cases. Patients occa- Having patients walk under conditions that challenge their
sionally have dysarthria (20%) as well as postural instability biomechanical, sensory, or cognitive resources can help better
(17%, n ¼ 55).5 The mean SARA score (as a global estimate of characterize the causes of their gait impairment.49 Typically,
cerebellar function) is approximately 15 points (higher in gait variability levels are higher in cerebellar ataxia compared
acquired forms [29 points] and lower in degenerative and with vestibular gait ataxia. In cerebellar syndromes, gait vari-
hereditary forms).5,43 About 30% of patients have additional ability is increased both during slow and fast walking, and in
clinical signs of polyneuropathy. Falls are frequently reported vestibular ataxia only during slow walking.50 The characteristic
in patients with chronic cerebellar dizziness and vertigo (50% pattern of gait variability in cerebellar patients indicates dis-
are recurrent fallers). The consequences of falls tend to be turbed integration of sensory feedback (during slow walking)
more severe. More than 30% of falls in patients with cerebel- and abnormal function of cerebellar pacemakers and feed-
lar syndromes result in injuries that require medical atten- forward coordination of multijoint movements (mostly during
tion. The odds ratio for falling is approximately 16-fold fast walking). Cerebellar pathologies that predominantly affect
higher than that in age-matched healthy controls.44 the flocculonodular lobe (such as DBN) show more prominent
gait variability during slow versus fast walking, which high-

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Laboratory Examinations of Posture and Gait lights the importance of the vestibulocerebellum for sensory
Quantitative posturography can demonstrate patterns consis- feedback mostly during slow walking51,52 (►Fig. 2). Gait vari-
tent with chronic forms of cerebellar dizziness and vertigo, but ability may be a surrogate marker to follow the clinical course of
these studies are not suitable to make a definitive diagnosis.45 the patient or measure the success of therapeutic interventions.
In posturography, patients with cerebellar dizziness and The quantification of gait variability has further important
vertigo show an increased body sway path in all directions and implications for the prediction of falls in patients with cerebel-
during all conditions (with and without multisensory pertur- lar syndromes. A recent study showed that high levels of gait
bation). A typical cerebellar 3-Hz sway is found in approxi- variability, especially during slow walking, are significantly
mately 15% of patients in the Fourier analysis of the frequency correlated with the risk of falling in patients with degenerative,
spectrum.45,46 In the rare subgroup of patients with ortho- hereditary, and sporadic forms of cerebellar disease.53
static tremor, who may present with a cerebellar phenotype in
ocular motor examination, a highly characteristic frequency Imaging and Genetics
peak is found between 14 and 18 Hz, which can be used to Every patient with newly diagnosed cerebellar dizziness or
prove the diagnosis.17 Artificial network-based posturo- vertigo should undergo a standardized diagnostic workup,
graphic analysis has high sensitivity and specificity in defining which includes imaging, laboratory testing, and, in certain
patients with cerebellar forms of dizziness and vertigo.46,47 cases, genetic testing. As the imaging modality of choice in
Patients with cerebellar syndromes show a typical patholog- acute cases, at least a computed tomographic (CT) scan and
ical gait pattern, which includes a broader base of support, CT angiography should be performed. Magnetic resonance
reduced step length, and high spatiotemporal variability of the (MR) diffusion- and perfusion-weighted imaging can add to

Fig. 2 Gait analysis and gait control in cerebellar ataxia. Patients with cerebellar ataxia (CA, left) have increased gait variability during slow and
fast walking compared with healthy subjects (HS, middle). Variability during slow walking () is determined by sensory integration, which is
mostly mediated by the vestibulocerebellum ( ), during fast walking ( ) by cerebellar pacemakers, which are located in the vermis ( ; right).
(Adapted from Schniepp et al.50,51)

Seminars in Neurology
 Cerebellar Dizziness and Vertigo Zwergal et al.

diagnostic accuracy.9 In recurrent and chronic forms of

cerebellar dizziness and vertigo, an MRI should be performed
to exclude cerebellar lesions, atrophy, or other structural
alterations. [18F]FDG-PET may be added if degenerative
forms of cerebellar syndrome are suspected. CSF analysis is
performed if potential paraneoplastic, autoimmune, or
infectious causes of cerebellar dysfunction need to be ruled
out or confirmed.20 If the phenotype and family history point
to a potential hereditary form of cerebellar syndrome,
genetic analysis can be considered. Selection of genes may
be adapted to the phenotype together with a specialist for
human genetics.18,20

Therapy
Therapy of patients with cerebellar dizziness and vertigo always
has to be multimodal and needs to include physical exercises for
eye stabilization, posture, gait control, occupational therapy for
limb function, and pharmacological treatments.54

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Pharmacotherapy
Aminopyridines, chlorzoxazone, and N-acetyl-DL-leucine
have shown beneficial effects in patients with cerebellar
dizziness and ocular motor disorders.55,56
A therapeutic effect of aminopyridines has been shown in
various forms of cerebellar dizziness and vertigo. In patients
with DBN, a significant reduction of the intensity was shown
by 3,4-diaminopyridine, 4-aminopyridine (4-AP), and the
sustained-release form fampridine (also known as
Ampyra or dalfampridine) in several randomized, controlled
trials.57–59 4-AP alleviates the symptoms of DBN, particularly
in patients with cerebellar atrophy; it reduces the slow-
phase velocity of DBN by half; and it improves visual acuity
and motor performance at a dosage of 5 to 10 mg four times a
day.60 Fampridine effectively reduces the intensity of DBN at
a dosage of 10 to 20 mg per day61 (►Fig. 3). 4-AP may also be
considered in patients with central positional nystagmus, as
has been demonstrated in single case reports.42 4-AP and
fampridine were successfully established as treatment
options in patients with EA2: they effectively reduced the
number of attacks and improved quality of life in patients Fig. 3 Effects of fampridine on downbeat nystagmus. (A) Original
recording of vertical eye position in a patient with DBN at baseline,
with EA2.62,63 Fampridine was also effective64 and is proba-
180 minutes after first drug administration, after 2 weeks of drug
bly similar to acetazolamide in reducing attacks in EA2 but administration, and after 4 weeks of washout. (B) Mean slow-phase
with fewer side effects. 4-AP also reduced gait variability and velocity (SPV) of 10 patients with DBN at baseline, 180 minutes after
frequency of falls in patients with degenerative and acquired first drug administration, after 2 weeks of drug administration, and
cerebellar syndromes.57 after 4 weeks of washout. SPV was significantly lower under medi-
cation than at baseline or after the washout period. (Adapted from
Chlorzoxazone, an activator of calcium-activated potassium
Claassen et al. 61)
channels, has been shown to improve postural stability in
patients with DBN at a dose of 500 mg three times per day in
a single non-controlled study.65 Physical Therapy
Finally, N-acetyl-DL-leucine, which has been used for The effect of physical therapy on cerebellar dizziness and
therapy of dizziness and vertigo in France since 1957, showed vertigo has not been specifically assessed in controlled trials.
a significant improvement of ataxia scores (namely, SARA However, there is indirect evidence that physical therapy
and SCAFI), gait variability, and quality of life at a dose of 5 g may be effective in these disorders.
per day in an observational study on patients with cerebellar A meta-analysis of interventional rehabilitation studies in
ataxia of various origins.66,67 Similar effects have been approximately 300 patients with hereditary cerebellar ataxia,
described for neurometabolic disorders with cerebellar dys- including coordination and balance training, cycling regimes,
function (such as Niemann-Pick disease type C).68 balance exercises with biofeedback, respiratory muscle training,

Seminars in Neurology
Cerebellar Dizziness and Vertigo Zwergal et al.

and treadmill training, showed statistically significant improve- M.S. is joint chief editor of the Journal of Neurology, editor
ment in at least one outcome measure of ataxia, gait, or in chief of Frontiers of Neuro-otology, and section editor of
balance.69 Although interventions were heterogeneous, multi- F1000. He has received speaker’s honoraria from Abbott,
modal rehabilitation programs with elements of balance train- Actelion, Auris Medical, Biogen, Eisai, Grünenthal, GSK,
ing, inpatient rehabilitation, and occupational therapy may be Henning Pharma, Interacoustics, Merck, MSD, Otometrics,
most effective. These interventions may improve function, Pierre-Fabre, TEVA, and UCB. He is a shareholder of Intra-
mobility, ataxia, and balance in degenerative cerebellar Bio. He acts as a consultant for Abbott, Actelion, Auris-
syndromes. These data are in line with effects of multimodal Medical, Heel, IntraBio, and Sensorion.
vestibular rehabilitation in patients with peripheral vestibular
disorders, which show a convincing effect on mobility, fall Acknowledgment
prevention, and quality of life.70,71 We thank Katie Göttlinger for copyediting the manuscript.

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