Differentials

Common

Vestibular neuritis/labyrinthitis

History

often preceded by upper respiratory tract infection; acute-onset true vertigo, nausea, vomiting; aggravated by head movement, gradually subsides in several days, mild dizziness and balance difficulty may persist; sensorineural hearing loss in the affected ear in labyrinthitis

Exam

peripheral vestibular nystagmus, a positive head impulse test to the side of peripheral vestibular loss, post-headshake nystagmus, deficits of coordination and gait

1st investigation
  • audiometry:

    unilateral sensorineural hearing loss in cases of labyrinthitis

  • caloric electronystagmography:

    caloric responses from the affected ear are reduced compared with the normal ear

    More
  • rotary chair testing:

    vestibulo-ocular reflex (VOR) gain may be normal or reduced at lower frequencies of rotation in poorly compensated cases; VOR phase lead and shortening of the VOR time constant to 6 to 12 seconds (normal >20 seconds)

    More
Other investigations
  • microbiological culture and sensitivity of middle ear effusions if present:

    positive if infectious cause

    More
  • serum fluorescent treponemal antibodies:

    raised antibodies are positive for syphilis

    More
  • serum, joint fluid, or cerebrospinal fluid antibodies to Borrelia detected by enzyme-linked immunosorbent assay (ELISA):

    raised antibodies to Borrelia on ELISA to detect Lyme disease

    More
  • CT temporal bones:

    fluid in the mastoid cells or a mass in the middle ear cavity if cholesteatoma is present

    More
  • MRI head:

    usually negative in vestibular disease but may show increased signal along the vestibular nerve or the labyrinths on the affected side; abnormal signal in the brainstem or cerebellum may indicate associated stroke and labyrinthine infarction

    More

Meniere disease

History

vertigo (at least two spontaneous episodes lasting 20 minutes to 12 hours within a single attack); fluctuating and unilateral aural symptoms (i.e., tinnitus, aural fullness and hearing loss)[8]

Exam

sensorineural hearing loss on Rinne or Weber testing, peripheral vestibular nystagmus is present during the attacks

1st investigation
  • audiometry:

    unilateral sensorineural hearing loss; usually low-frequency hearing loss is present in early stages and during or before attacks; as disease progresses, middle and high frequencies are affected

    More
Other investigations
  • electrocochleography:

    abnormally large summating potential amplitude relative to the action potential amplitude

  • vestibular evoked myogenic potentials (VEMP):

    increased amplitude in early disease; attenuated or absent in later stages

    More

Vitamin B1 (thiamine) deficiency

History

history of chronic alcoholism, anorexia nervosa, hyperemesis gravidarum, gastrointestinal surgery, systemic malignancy, renal dialysis, or infections such as AIDS; imbalance and ataxic gait; nystagmus, abnormal ocular motility, cognitive impairment

Exam

bilateral or unilateral peripheral vestibular hypofunction features ataxic gait, positive head impulse to both sides, poor dynamic visual acuity, sway on Romberg testing; Wernicke encephalopathy features ataxic gait, nystagmus (usually horizontal gaze evoked to both sides), ocular motility disturbance, cognitive impairment

1st investigation
  • erythrocyte thiamine pyrophosphate:

    low

Other investigations
  • vestibular testing:

    reduced caloric responses; reduced vestibulo-ocular reflex (VOR) gain, VOR phase lead, and shortening of the VOR time constant indicating unilateral or bilateral peripheral vestibular hypofunction

  • MRI brain:

    bilateral increased T2 signal in the paraventricular regions of the thalamus, hypothalamus, mamillary bodies, periaqueductal region, fourth ventricle floor, and midline cerebellum

    More

Ototoxic vestibulopathy

History

progressive ataxic gait and oscillopsia shortly following exposure to ototoxic medication; may be accompanied by progressive bilateral hearing loss; balance usually worsens when walking in dim light or with eyes closed

Exam

poor dynamic visual acuity, bilateral positive head impulse tests, ataxic gait, poor tandem walk, sway on Romberg testing

1st investigation
  • audiometry:

    sensorineural hearing loss may be associated with vestibulopathy from aminoglycoside ototoxicity

Other investigations
  • caloric electronystagmography:

    Bilaterally reduced or absent caloric responses

    More
  • rotary chair testing:

    very low vestibulo-ocular reflex (VOR) gain, marked VOR phase lead, and marked shortening of the VOR time constant to <6 seconds

  • blood aminoglycoside levels:

    elevated aminoglycoside blood levels or a history of them may be indicative but ototoxicity can also occur with therapeutic levels

Benign paroxysmal positional vertigo (canalithiasis)

History

recurring, brief vertigo precipitated by specific positional change such as tilting the head, lying down, or rolling over in bed, with no associated auditory or neurologic symptoms

Exam

Dix-Hallpike maneuver resulting in vertigo with torsional, vertical nystagmus after a latency of several seconds (a positive result) confirms benign paroxysmal positional vertigo (BPPV) involving the posterior semicircular canal on the tested side; if the Dix-Hallpike maneuver is negative then perform the supine roll test to assess for lateral semicircular canal BPPV[11]

1st investigation
  • clinical diagnosis:

    vertigo with the appropriate position-provoked nystagmus response on positional maneuvers

Other investigations

    Hemorrhagic stroke

    History

    history of hypertension; acute-onset ataxia and dizziness, headache, vision loss, diplopia, dysarthria, dysphagia, sensory symptoms, and weakness involving the limbs; may progress to altered level of consciousness

    Exam

    altered level of consciousness, ocular motility disturbance, nystagmus, pupillary abnormalities such as Horner syndrome, dysarthric speech, abnormal gag reflex, sensory loss, pyramidal weakness. Central nrevous system (CNS) findings on HINTS exam (normal vestibular-ocular reflex, direction-changing gaze-evoked nystagmus and vertical correction on alternate eye cover test)

    1st investigation
    • CT brain:

      intracranial hemorrhage

      More
    Other investigations

      Ischemic stroke

      History

      history of vascular disease; acute-onset ataxia, dizziness, vision loss, diplopia, dysarthria, dysphagia, sensory symptoms, weakness involving the limbs; may progress to altered level of consciousness

      Exam

      altered level of consciousness, ocular motility disturbance, nystagmus, pupillary abnormalities such as Horner syndrome, dysarthric speech, abnormal gag reflex, sensory loss, pyramidal weakness. Central CNS findings on HINTS exam (normal vestibular-ocular reflex, direction-changing gaze-evoked nystagmus and vertical correction on alternate eye cover test)

      1st investigation
      • MRI brain:

        evidence of infarction

        More
      Other investigations
      • angiography (conventional computed tomography angiography or magnetic resonance angiography):

        vertebrobasilar artery stenosis or dissections

      Alcohol-related cerebellar degeneration

      History

      chronic history of alcohol abuse (>10 years); usually gradual onset of imbalance and impaired gait, although sudden onset or acute worsening may occur; tremor, dysarthria, and loss of coordination of arms in a minority of cases only

      Exam

      signs of midline cerebellar dysfunction: abnormal stance, ataxic gait, inability to perform tandem walk, poor heel-shin testing, mildly abnormal finger-nose testing; postural tremor of arms and dysarthria in a minority of cases; nystagmus, abnormal ocular motility, and cognitive impairment if co-existing Wernicke encephalopathy; vertigo is not a feature

      1st investigation
      • CT brain:

        may show cerebellar hemisphere and vermis atrophy

      • MRI brain:

        may show cerebellar hemisphere and vermis atrophy

      Other investigations

        Vestibular migraine

        History

        diagnostic criteria are based on a history of migraine with at least 5 episodes fulfilling the following criteria: vestibular symptoms of moderate or severe intensity, lasting between 5 minutes and 72 hours, a temporal association between vestibular and migraine symptoms during at least half of the episodes, and exclusion of other causes

        Exam

        young and middle-aged patients with vertigo, headache, nausea, and low-velocity, sustained, positional nystagmus that dissipates as the patient becomes asymptomatic is highly suggestive of vestibular migraine; spontaneous and head shake nystagmus is seen in some episodes of vestibular migraine

        1st investigation
        • clinical diagnosis:

          low-velocity, sustained nystagmus on positional testing when symptoms are present

          More
        Other investigations

          Idiopathic Parkinson disease

          History

          falls, slowing of movements, difficulty initiating movements, difficulty standing up from a chair or turning while walking, resting tremor

          Exam

          bradykinesia, slow shuffling gait, flexed posture, decrease arm swing, postural instability, Myerson sign, mask facies, hypophonic voice, rigid tone with cogwheeling, pill rolling tremor, hypometric saccades; repetitive finger movements are slow and with reduced amplitude

          1st investigation
          • no initial test:

            clinical diagnosis

          • dopaminergic agent trial:

            improvement in symptoms

            More
          Other investigations
          • functional neuroimaging:

            assess integrity of nigrostriatal projections in Parkinson disease

            More

          Peripheral neuropathy

          History

          numbness in the lower extremities, paresthesiae, dysesthesias, lower extremity weakness, difficulty with gait, falls, may have history of diabetes mellitus

          Exam

          loss of proprioception and sensation in the lower extremities, sensory ataxia, lower extremity weakness, difficulty with gait, Rhomberg positive

          1st investigation
          • nerve conduction studies/electromyography (EMG):

            demyelinating neuropathies: dispersion of the compound muscle action potentials, marked slowing of conduction velocity, conduction block, delay in F waves, absent H reflex; axonal neuropathies: compound muscle action potentials with low amplitude, mild slowing of conduction velocity, EMG may show fibrillation potentials and increased insertional activity

            More
          Other investigations
          • chest x-ray:

            in selected cases to exclude infection/malignancy

          • fasting blood glucose:

            may be raised in diabetic peripheral neuropathy

          • serum autoantibodies (antinuclear antibodies or antineutrophil cytoplasmic antibodies):

            in selected cases to exclude collagen vascular disease

          • serum vitamin B12 and folate levels:

            in selected cases to exclude subacute combined degeneration of the spinal cord and folate deficiency

          • genetic testing for Charcot-Marie-Tooth disease type 1:

            in selected cases to exclude hereditary peripheral neuropathy

          Uncommon

          Vestibular schwannoma (acoustic neuroma)

          History

          unilateral hearing loss, dizziness, balance difficulty; with larger tumors there may be sensory symptoms over the face or facial weakness on the affected side; may occur sporadically or in bilateral cases as part of von Recklinghausen neurofibromatosis

          Exam

          sensorineural hearing loss on the affected side, chronic unilateral peripheral vestibular loss, a positive head-impulse test, post-headshake nystagmus, poor dynamic visual acuity; nonspecific deficits in balance, gait; tandem walk; Romberg sway

          1st investigation
          • MRI temporal bones:

            an enhancing mass along the eighth cranial nerve that may be intracanalicular or extend to the cerebellopontine angle

            More
          • audiometry:

            sensorineural hearing loss

          • auditory evoked brainstem responses (ABR):

            latencies of waves III and V are prolonged on the affected side

            More
          Other investigations
          • caloric electronystagmography:

            caloric responses from the affected ear are reduced compared with the normal ear

            More
          • rotary chair testing:

            vestibulo-ocular reflex (VOR) gain may be normal or reduced at lower frequencies of rotation in poorly compensated cases; VOR phase lead and shortening of the VOR time constant to 6-12 seconds (normal >20 seconds)

            More
          • surgical excision:

            histopathologic diagnosis of the tumor

            More

          Sequential bilateral vestibular neuritis

          History

          remote episode of vertigo with complete resolution of symptoms followed by a more recent episode of dizziness, resulting in persisting disequilibrium and imbalance; the first episode results in peripheral vestibular loss that is compensated leading to resolution of symptoms, whereas the second episode results in peripheral vestibular loss involving the fellow ear; oscillopsia or blurring of vision with head movement may result from a deficiency vestibulo-ocular reflex

          Exam

          poor dynamic visual acuity, bilateral positive head impulse tests, ataxic gait, poor tandem walk, sway on Romberg testing

          1st investigation
          • caloric electronystagmography:

            Bilaterally reduced caloric responses

            More
          • rotary chair testing:

            very low VOR gain, marked VOR phase lead, and marked shortening of the VOR time constant to <6 seconds

          Other investigations
          • serum fluorescent treponemal antibodies:

            raised antibodies are positive for syphilis

            More
          • serum, joint fluid, or cerebrospinal fluid antibodies to Borrelia detected by enzyme-linked immunosorbent assay (ELISA):

            raised antibodies to Borrelia on ELISA to detect Lyme disease

            More
          • MRI brain:

            exclude brainstem/cerebellar infarcts

            More

          Idiopathic bilateral vestibular hypofunction

          History

          progressive ataxic gait and oscillopsia accompanied by progressive bilateral hearing loss; balance usually worsens when walking in dim light or with eyes closed; no history of prior inner ear disease such as vestibular neuritis to explain the peripheral vestibular loss

          Exam

          poor dynamic visual acuity, bilateral positive head impulse tests, ataxic gait, poor tandem walk, sway on Romberg testing

          1st investigation
          • audiometry:

            may show co-existing bilateral sensorineural hearing loss

          • caloric electronystagmography:

            Bilaterally reduced caloric responses

            More
          • rotary chair testing:

            very low vestibulo-ocular reflex (VOR) gain, marked VOR phase lead, and marked shortening of the VOR time constant to <6 seconds

          Other investigations
          • MRI brain:

            exclude bilateral vestibular schwannomas

          • serum fluorescent treponemal antibodies:

            raised antibodies are positive for syphilis

            More
          • serum, joint fluid, or cerebrospinal fluid antibodies to Borrelia detected by enzyme-linked immunosorbent assay (ELISA):

            raised antibodies to Borrelia on ELISA to detect Lyme disease

            More

          Congenital bilateral vestibular hypofunction

          History

          ataxic gait and oscillopsia that may be accompanied by congenital bilateral hearing loss; balance usually worsens when walking in dim light or with eyes closed; symptoms and signs are milder than in acquired cases of bilateral peripheral vestibular loss; may present as “always having been a little off balance

          Exam

          poor dynamic visual acuity, bilateral positive head impulse tests, gait may be normal, poor tandem walk, sway on Romberg testing

          1st investigation
          • audiometry:

            may show co-existing bilateral sensorineural hearing loss

          • caloric electronystagmography:

            Bilaterally reduced caloric responses

            More
          • rotary chair testing:

            very low vestibulo-ocular reflex (VOR) gain, marked VOR phase lead, and marked shortening of the VOR time constant to <6 seconds

          Other investigations
          • MRI brain:

            exclude bilateral vestibular schwannomas

          • serum fluorescent treponemal antibodies:

            raised antibodies are positive for syphilis

            More
          • serum, joint fluid, or cerebrospinal fluid antibodies to Borrelia detected by enzyme-linked immunosorbent assay (ELISA):

            raised antibodies to Borrelia on ELISA to detect Lyme disease

            More

          Degenerative (age-related) inner ear disease

          History

          chronic slowly progressive ataxic gait and oscillopsia, which may be accompanied by progressive bilateral hearing loss (presbycusis); balance usually worsens when walking in dim light or with eyes closed

          Exam

          poor dynamic visual acuity, bilateral positive head impulse tests, ataxic gait, poor tandem walk, sway on Romberg testing; may rarely be accompanied by signs of cerebellar dysfunction[19]

          1st investigation
          • audiometry:

            usually shows associated bilateral high frequency sloping sensorineural hearing loss typical of presbycusis

          • caloric electronystagmography:

            Bilaterally reduced caloric responses

            More
          • rotary chair testing:

            very low vestibulo-ocular reflex (VOR) gain, marked VOR phase lead, and marked shortening of the VOR time constant to <6 seconds

          Other investigations
          • MRI brain:

            exclude bilateral vestibular schwannomas

          • serum fluorescent treponemal antibodies:

            raised antibodies are positive for syphilis

            More
          • serum, joint fluid, or cerebrospinal fluid antibodies to Borrelia detected by enzyme-linked immunosorbent assay (ELISA):

            raised antibodies to Borrelia on ELISA to detect Lyme disease

            More

          Autoimmune inner ear disease

          History

          progressive bilateral sensorineural hearing loss and dizziness that may be similar to bilateral simultaneous Meniere disease, corneal involvement (eye pain and photophobia), and systemic symptoms resulting from vasculitis; may occur with Cogan syndrome and may be associated with another autoimmune disease

          Exam

          bilateral hearing loss, peripheral vestibular nystagmus, slit lamp exam is essential to exclude interstitial keratitis (Cogan syndrome)

          1st investigation
          • audiometry:

            rapidly progressive fluctuating bilateral sensorineural hearing loss

          • CBC:

            may show anemia

          • erythrocyte sedimentation rate and CRP:

            elevated

          • antinuclear antibodies, rheumatoid factor, antineutrophil cytoplasmic antibodies, C1Q immune complex:

            elevated

          • vestibular testing:

            bilateral peripheral vestibular loss

          Other investigations
          • serum fluorescent treponemal antibodies:

            exclude infectious cause

          • serum, joint fluid, or cerebrospinal fluid antibodies to Borrelia detected by enzyme-linked immunosorbent assay (ELISA):

            raised antibodies to Borrelia on ELISA to detect Lyme disease

            More
          • MRI brain:

            exclude bilateral vestibular schwannomas

          • antithyroid (thyroglobulin and microsomal) antibodies:

            elevated in cases associated with thyroid disease

          • anti-HSP70 antibodies:

            may be elevated

            More
          • antigliadin and antiendomysial antibodies:

            elevated in celiac disease

          Superior canal dehiscence (SCD)

          History

          brief dizziness precipitated by coughing, sneezing, straining, or sudden loud noise; autophony; feeling that the affected ear is blocked

          Exam

          dizziness and nystagmus can be precipitated by fistula test, tragal compression, Valsalva, or loud noise (Tullio phenomenon)

          1st investigation
          • vestibular evoked myogenic potentials (VEMP):

            reduced thresholds (or larger VEMPs)

            More
          • high-resolution CT temporal bones:

            views in Poschl and Stenvers planes show SCD[52]

            More
          Other investigations
          • audiometry:

            bone conduction scores are better than air conduction (conductive hyperacusis)

            More
          • tympanometry:

            may induce dizziness

            More
          • fistula test:

            Valsalva or the fistula test of the affected ear precipitate brief dizziness associated with nystagmus

            More
          • MRI temporal bones:

            may exclude other unilateral diseases affecting the middle ear such as tumor

            More

          Meningitis

          History

          bacterial meningitis presents acutely with fever, altered mental state, and headache, dizziness, balance difficulty, and hearing loss and may follow syphilis, Lyme disease, or fungal infection

          Exam

          fever, nuchal rigidity, and altered mental status; poor dynamic visual acuity, positive head impulse tests; unsteady gait, poor tandem walk, sway on Romberg testing

          1st investigation
          • cerebrospinal fluid (CSF) examination:

            raised CSF pressure; lymphocytosis or polymorphonuclear leukocytes; raised protein in bacterial infection; specific pathogen isolated

            More
          Other investigations
          • caloric electronystagmography:

            caloric responses may be reduced in one or both ears

          • rotary chair testing:

            low vestibulo-ocular reflex (VOR) gain, VOR phase lead, and shortening of the time constant with peripheral vestibular loss

          • audiometry:

            sensorineural hearing loss may be present

          Mal de debarquement syndrome

          History

          persisting disequilibrium with onset after an ocean cruise or other prolonged travel;[22] disequilibrium is most severe when sitting still or lying down

          Exam

          examination is normal or shows nonspecific deficits in balance (e.g., difficulty with tandem walk)

          1st investigation
          • no testing required:

            clinical diagnosis

          Other investigations

            Spinocerebellar ataxia

            History

            usually begins in childhood; progressive ataxia, motor difficulty, tremor, cognitive decline, vision loss, cognitive dysfunction, seizures, myoclonus, dysarthria, sensory symptoms, vomiting, and gastrointestinal pain depending on the genetic type

            Exam

            nystagmus, gaze-evoked nystagmus, slow saccades, upper motor neuron signs, macular degeneration, tremor, myoclonus, and cognitive impairment[18]

            1st investigation
            • genetic testing:

              mutation detected

              More
            Other investigations

              Multiple sclerosis (MS)

              History

              variable presentation: multiple episodes separated by space (i.e., neurological symptoms result from lesions in different central nervous system sites) and time; painful unilateral visual loss, sensory disturbances, progressive limb weakness, gait difficulty, ataxia, loss of balance, paroxysmal vertigo

              Exam

              coexisting signs of brainstem/cerebellar dysfunction or of myelopathy, which suggests a multifocal disease

              1st investigation
              • MRI brain and spinal cord:

                hyperintensities in the periventricular white matter; areas of demyelination in the spinal cord

                More
              Other investigations
              • lumbar puncture with cerebrospinal fluid examination:

                glucose and protein should be normal; cell count may be slightly elevated but never above 50/microliter; oligoclonal bands and elevated CSF IgG usually present

                More

              Cerebellitis/brainstem encephalitis

              History

              headache, acute vertigo, ataxia, nausea, vomiting; may present as a post-infectious disorder, as a paraneoplastic syndrome, or as part of an inflammatory disorder[16]

              Exam

              gaze-evoked nystagmus, downbeat nystagmus, rebound nystagmus, saccadic dysmetria, ocular flutter, dysarthria/scanning speech, limb dysmetria, wide-based ataxic gait, signs of raised intracranial pressure

              1st investigation
              • cerebrospinal fluid (CSF) protein, glucose, and white cell count:

                mildly elevated protein (60 to 80 mg/dL), normal glucose, and a moderate mononuclear cell leukocytosis (up to 1000 leukocytes/microL)

                More
              • CSF virology:

                findings from CSF cultures for enteroviruses, mumps, and certain arboviruses may be positive

                More
              Other investigations
              • CSF immunoglobulin detection by enzyme-linked immunosorbent assay:

                raised IgM detection early in viral infection with West Nile virus and IgG in dengue

                More
              • CT brain:

                edema, hemorrhages, low-density viral lesions, hydrocephalus, and herniation

              • MRI brain:

                encephalitis results in cerebral edema, which can readily be seen on MRI as increased signal

                More
              • electroencephalogram:

                may show diffuse activity in some of the viral encephalitides

              Wernicke encephalopathy

              History

              bilateral vestibulopathy, nystagmus, ophthalmoparesis, ataxia, change in mental status, history of alcohol abuse or of protracted vomiting (e.g., hyperemesis gravidarum)

              Exam

              confusion, memory difficulty, confabulation, ophthalmoplegia, nystagmus, positive head impulse tests, ataxic gait, poor tandem walk, sway on Romberg testing

              1st investigation
              • MRI brain:

                increased density of the mammillary bodies and periaqueductal grey matter

                More
              Other investigations
              • blood erythrocyte transketolase levels:

                raised levels detect thiamine deficiency

                More
              • blood glucose levels:

                exclude hypoglycemia and hyperglycemia

              • CT brain:

                may be normal or show symmetrical periventricular low-density abnormalities, which are uncommon in other disorders

                More

              Posterior fossa tumor

              History

              disequilibrium, ataxic gait, limb ataxia, dysarthria, oscillopsia, headache

              Exam

              gaze-evoked nystagmus, downbeat nystagmus, rebound nystagmus, saccadic dysmetria, ocular flutter, dysarthria/scanning speech, limb dysmetria, wide-based ataxic gait, sway on Romberg testing

              1st investigation
              • MRI brain:

                tumor visualized

              Other investigations
              • brain biopsy/surgical excision:

                brain smear, biopsy, or surgical excision allows for histopathologic diagnosis

              Chiari malformation

              History

              balance difficulty and positional dizziness

              Exam

              downbeat nystagmus, most prominent on lateral gaze; positional testing may precipitate dizziness with downbeat nystagmus

              1st investigation
              • MRI brain/spine:

                craniocervical junction lesion

              Other investigations

                Central pontine myelinosis

                History

                occurs in the setting of rapid correction of hyponatremia; acute paraplegia or quadriplegia associated with diplopia, dysarthria, and dysphagia; may progress to locked-in syndrome

                Exam

                abnormal ocular motility especially involving horizontal eye movements, progressive paralysis, dysarthric speech, loss of consciousness

                1st investigation
                • MRI brain:

                  abnormal signal in the pons on T2 images

                Other investigations

                  Paraneoplastic syndrome

                  History

                  symptoms may be rapid or slowly progressive, ataxia with loss of coordination of limbs and dysarthria; commonly associated malignancies include small cell lung cancer, breast cancer, ovarian cancer, uterine cancer, and Hodgkin lymphoma

                  Exam

                  vestibulo-cerebellar dysfunction resulting in progressive ataxic gait, marked truncal ataxia, vertical nystagmus, and dysarthria

                  1st investigation
                  • anti-Yo antibodies:

                    positive in cerebellar degeneration​

                  • anti-Ri antibodies:

                    positive in cerebellar ataxias​

                  • anti-Ma antibodies:

                    positive in cerebellar or brainstem dysfunction​

                  Other investigations

                    Vitamin E deficiency

                    History

                    progressive gait difficulty, ataxia associated with weakness and visual field loss, dementia, cardiac arrhythmias; consider in people with cystic fibrosis, gastrointestinal disease, and abetalipoproteinemia

                    Exam

                    ataxia, hyporeflexia, visual field constriction, upgaze palsy, limb dysmetria, muscle weakness, diminished proprioception, pigmentary retinopathy

                    1st investigation
                    • serum alpha-tocopherol level:

                      decreased​

                    Other investigations

                      Celiac disease

                      History

                      variable gastrointestinal symptoms (diarrhea, bloating, abdominal discomfort, weight loss), fatigue; neurological complications of celiac disease include ataxia, peripheral neuropathy, dementia, and seizures

                      Exam

                      anemia, dermatitis herpetiformis (pruritic papulovesicular lesions over the extensor surfaces of the arms and legs), ataxia, hyporeflexia, limb dysmetria, muscle weakness, diminished proprioception

                      1st investigation
                      • immunoglobulin A-tissue transglutaminase titer:

                        elevated​

                      • endomysial antibody:

                        elevated

                      Other investigations
                      • small bowel biopsy and histologic examination:

                        villous atrophy on histology

                      Primary cerebellar degeneration

                      History

                      typically late-onset chronic progressive ataxic gait with earlier onset in familial cases; may, rarely, be accompanied by bilateral peripheral vestibular hypofunction

                      Exam

                      wide-based ataxic gait, downbeat nystagmus, gaze-evoked nystagmus, saccadic pursuit, dysarthria, limb dysmetria, and dysdiadochokinesia, bilateral head impulse tests with poor dynamic visual acuity if co-existing bilateral peripheral vestibular loss

                      1st investigation
                      • CT or MRI brain:

                        may show cerebellar atrophy

                        More
                      Other investigations
                      • serum methylmalonic acid and homocysteine:

                        elevated levels

                        More
                      • anti-Yo antibodies:

                        positive in cerebellar degeneration​

                        More
                      • anti-Ri antibodies:

                        positive in cerebellar ataxias​

                        More
                      • anti-Ma antibodies:

                        positive in cerebellar or brainstem dysfunction​

                        More
                      • serum alpha-tocopherol:

                        decreased level

                        More
                      • serum HIV enzyme-linked immunosorbent assay:

                        positive in HIV infection

                        More

                      Secondary parkinsonism

                      History

                      acute or subacute onset, secondary to stroke or drug, focal weakness, sensory symptoms, cognitive decline

                      Exam

                      bradykinesia, slow shuffling gait, flexed posture, decrease arm swing, postural instability, Myerson sign, mask facies, hypophonic voice, rigid tone with cogwheeling, pill rolling tremor, hypometric saccades; repetitive finger movements are slow and with reduced amplitude

                      1st investigation
                      • CT or MRI brain:

                        may detect lesion or infarct

                        More
                      Other investigations

                        Normal pressure hydrocephalus

                        History

                        progressive cognitive decline with gait difficulty and urinary incontinence

                        Exam

                        gait may be ataxic or may have magnetic gait, cognitive decline, parkinsonian features

                        1st investigation
                        • MRI brain:

                          enlargement of ventricles associated with transependymal edema​

                        Other investigations

                          Corticobasal degeneration

                          History

                          progressive gait difficulty associated with motor dysfunction and alien hand syndrome

                          Exam

                          may have signs of parkinsonism associated with dystonia, myoclonus, alien hand syndrome, and cognitive decline including involvement of language function

                          1st investigation
                          • MRI brain:

                            asymmetric frontoparietal atrophy

                          Other investigations

                            Progressive supranuclear palsy

                            History

                            progressive gait difficulty with speech and swallowing affected; parkinsonism with early falls

                            Exam

                            vertical gaze palsy, pseudobulbar palsy, early postural instability

                            1st investigation
                            • MRI brain:

                              sagittal views may show midbrain atrophy resulting in morphology resembling a hummingbird; midbrain/pons ratio may be reduced​

                            Other investigations

                              Multiple system atrophy (MSA; striatonigral degeneration, Shy-Drager syndrome)

                              History

                              rigidity, bradykinesia, tremor, gait difficulty, poor response to levodopa, erectile dysfunction, urinary symptoms, coordination difficulty; postural hypotension is seen in Shy-Drager syndrome

                              Exam

                              rigidity, bradykinesias, hypophonic voice, slow shuffling gait, tremor, myoclonus, orthostatic hypotension, ocular dysmetria, gaze evoked nystagmus, saccadic pursuit, ataxic gait; limb ataxia from cerebellar involvement

                              1st investigation
                              • no testing required:

                                clinical diagnosis

                                More
                              Other investigations

                                Spinal cord trauma

                                History

                                acute limb weakness, sensory loss, and sphincter dysfunction following trauma

                                Exam

                                upper motor neuron signs (corticospinal tract lesions), lower motor neuron signs (cervical or lumbar spine lesions): muscle atrophy, muscle fasciculations, hyporeflexia, muscle weakness; sensory signs: loss of joint position sense (posterior column lesions), loss of temperature and pinprick sensation (spinothalamic tract lesions), loss of reflexes

                                1st investigation
                                • CT spine:

                                  particularly useful to evaluate bony abnormalities of the spine

                                  More
                                • MRI spine:

                                  detects trauma, tumor, hemorrhage, abscess

                                  More
                                Other investigations

                                  Guillain-Barre syndrome (GBS)

                                  History

                                  acute progressive balance difficulty, ascending weakness and areflexia, numbness and paresthesias of extremities, ataxic gait, limb weakness, constipation, bladder symptoms, orthostatic lightheadedness; may have diplopia with the Miller Fisher variant; history of upper respiratory infection or diarrhea preceding onset of symptoms supports diagnosis of GBS

                                  Exam

                                  muscle atrophy and fasciculations, muscle weakness, hyporeflexia or areflexia, ataxia, ophthalmoplegia, pupillary dilation with the Miller Fisher variant

                                  1st investigation
                                  • nerve conduction studies/electromyography (EMG):

                                    demyelinating neuropathies: dispersion of the compound muscle action potentials, marked slowing of conduction velocity, conduction block, delay in F waves, absent H reflex; axonal neuropathies: compound muscle action potentials with low amplitude, mild slowing of conduction velocity, EMG may show fibrillation potentials and increased insertional activity; Miller Fisher syndrome: absent or reduced sensory responses[60]

                                    More
                                  Other investigations
                                  • GQ1b antibody test:

                                    positive if GBS with ophthalmoplegia[30][61][62]​​

                                  • cerebrospinal fluid (CSF) protein:

                                    elevated (45 to 200 mg/dL in 73% of cases but may exceed 1000 mg/dL)[63]

                                    More

                                  Spinal spondylosis

                                  History

                                  weakness, numbness, paresthesias, gait and coordination difficulty, neck pain and stiffness

                                  Exam

                                  limited range of motion of neck, signs of myelopathy, pyramidal distribution weakness, spastic tone, hyperreflexia, Hoffmann sign, extensor plantar responses, loss of joint position sense in the lower extremities, unsteady gait

                                  1st investigation
                                  • MRI cervical spine:

                                    spondylosis and spinal stenosis with myelopathy (abnormal cord signal)

                                  Other investigations

                                    Spinal cord tumor

                                    History

                                    progressive myelopathy that may be associated with back pain

                                    Exam

                                    signs of myelopathy and or radiculopathy

                                    1st investigation
                                    • MRI spine:

                                      mass and spinal cord involvement

                                    Other investigations
                                    • chest x-ray:

                                      lung mass if lung cancer is the primary

                                    • mammogram:

                                      breast mass if breast cancer is the primary

                                    • prostate-specific antigen:

                                      elevated if prostate cancer is the primary

                                    Neuromyelitis optica (NMO)

                                    History

                                    history of MS, ascending sensory symptoms to trunk, sphincter disturbance, vision loss from optic neuritis (ON), diplopia, dysarthria and coordination difficulty due to cerebellar involvement, fatigue and cognitive difficulty

                                    Exam

                                    spastic muscle tone, hyperreflexia, pyramidal distribution weakness, extensor plantar responses, sensory loss, sway on Romberg testing, loss of anal sphincter tone, vision loss, cerebellar dysfunction, internuclear ophthalmoplegia, nystagmus, monocular vision loss

                                    1st investigation
                                    • MRI brain:

                                      swelling of optic nerve; enhancement in optic nerve; white matter lesions in patients with MS or at risk of MS

                                    Other investigations
                                    • aquaporin-4 (AQP4) antibody, myelin oligodendrocyte glycoprotein (MOG) antibody, and collapsin response mediator protein 5 (CRMP5) antibody:

                                      may be positive

                                      More
                                    • cerebrospinal fluid evaluation:

                                      oligoclonal bands; high IgG index

                                      More

                                    Subacute combined degeneration of the cord

                                    History

                                    gait difficulty associated with weakness and numbness of limbs, Lhermitte symptom from posterior column involvement in the cervical cord, optic neuropathy, cognitive decline associated with pernicious anemia, gastric bypass surgery, nutritional deficiency, Crohn disease, Whipple disease, Zollinger-Ellison syndrome

                                    Exam

                                    pyramidal weakness, hyperreflexia, extensor plantar responses, loss of proprioception in limbs

                                    1st investigation
                                    • serum methylmalonic acid and homocysteine levels:

                                      elevated levels are diagnostic of vitamin B12 deficiency[66]

                                    Other investigations
                                    • blood film:

                                      macrocytic anemia and hypersegmented neutrophils

                                    • serum vitamin B12:

                                      usually reduced but may be normal in deficiency states

                                    Syphilis, tabes dorsalis

                                    History

                                    history of syphilis infection, lancinating pain, or gastric crisis

                                    Exam

                                    Argyll Robertson pupils

                                    1st investigation
                                    • serum fluorescent treponemal antibody absorption (FTA-ABS) and microhemagglutination treponema pallidum (MHA-TP):

                                      reactive

                                      More
                                    Other investigations
                                    • cerebrospinal fluid (CSF) cytology:

                                      may be normal or show mild lymphocytic pleocytosis (10 to 50 cells/microL) with increased protein (45 to 75 mg/dL or higher)

                                    • CSF serology:

                                      CSF VDRL may be nonreactive in up to 25% of cases; CSF FTA-ABS is reactive in neurosyphilis

                                      More

                                    Tuberculosis of the spine (Pott disease)

                                    History

                                    myelopathy with back pain, history of tuberculosis (TB) infection

                                    Exam

                                    may have signs of myelopathy (upper motor neuron and sensory loss to sensory level on trunk)

                                    1st investigation
                                    • chest x-ray:

                                      consolidation, pulmonary infiltrates, mediastinal or hilar lymphadenopathy, upper zone fibrosis

                                      More
                                    • MRI spine:

                                      compressive spinal lesions

                                    • sputum acid-fast bacilli smear and culture:

                                      presence of acid-fast bacilli (Ziehl-Neelsen stain) in specimen; testing of three specimens (minimum 8 hours apart, including an early morning specimen) is recommended in many countries; consult local guidance[69]

                                      More
                                    • acid-fast bacilli smear and culture of extrapulmonary biopsy specimen:

                                      positive

                                      More
                                    • nucleic acid amplification tests (NAAT):

                                      positive for M tuberculosis

                                      More
                                    Other investigations
                                    • lateral flow urine lipoarabinomannan (LF-LAM) assay:

                                      positive

                                      More

                                    HIV infectious myelopathy

                                    History

                                    history of HIV infection; progressive spastic weakness with sensory symptoms and sphincter dysfunction

                                    Exam

                                    weakness, sensory deficits, sphincter dysfunction, signs of myelopathy without distinct sensory level

                                    1st investigation
                                    • serum HIV enzyme-linked immunosorbent assay:

                                      positive in HIV infection

                                    Other investigations
                                    • MRI spine:

                                      non-enhancing high signal areas present on multiple contiguous slices, which can involve posterior columns or be diffuse

                                    Human T-lymphotropic virus (HTLV)-1 infectious myelopathy

                                    History

                                    progressive spastic weakness with sensory symptoms and sphincter dysfunction; affects adults from equatorial areas of the world; myelopathy may be associated with uveitis, arthritis, polymyositis, keratoconjunctivitis, and pulmonary lymphocytic alveolitis

                                    Exam

                                    uveitis, keratoconjunctivitis, joint swelling

                                    1st investigation
                                    • cerebrospinal fluid (CSF) polymerase chain reaction for HTLV-1 antigen:

                                      positive

                                      More
                                    Other investigations

                                      Systemic lupus erythematosus (SLE) inflammatory myelopathy

                                      History

                                      history of SLE, malar rash, vasculitis, myocarditis

                                      Exam

                                      spastic paraparesis, sphincter disturbance, and sensory loss (acute transverse myelitis)

                                      1st investigation
                                      • antinuclear antibodies (ANA):

                                        positive

                                        More
                                      Other investigations
                                      • anti-dsDNA and anti-Smith antibodies:

                                        elevated titre

                                        More
                                      • MRI spine:

                                        may demonstrate intramedullary spinal lesions

                                      Anxiety disorder

                                      History

                                      anxiety, dizziness or faintness, palpitations, sweating, trembling or shaking, fear of dying, paresthesiae, chills or hot flushes, breathlessness or choking sensation

                                      Exam

                                      hyperventilation, rapid pulse rate, exam otherwise normal

                                      1st investigation
                                        Other investigations
                                        • ECG:

                                          normal

                                        • chest x-ray:

                                          normal

                                        Drug toxicity

                                        History

                                        dizziness, faintness, deafness, nausea, history of medication for anxiety, epilepsy, ischemic heart disease, hypertension, malignancy

                                        Exam

                                        common drugs include aminoglycosides, methotrexate, cisplatin, tranquilizers, barbiturates, antihistamines, antihypertensives, diuretics, amiodarone

                                        1st investigation
                                          Other investigations
                                          • urine drug toxicity screen:

                                            raised levels of drugs and their metabolites

                                          • blood drug toxicity screen:

                                            raised levels of drugs and their metabolites

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