Friedreich Ataxia Workup

Updated: May 04, 2021
  • Author: Jasvinder Chawla, MD, MBA; Chief Editor: Selim R Benbadis, MD  more...
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Workup

Laboratory Studies

Genetic counseling is available for prenatal diagnosis of Friedreich ataxia (FA) for parents with one affected child. Population screening for carriers of the defective gene is not practical. A specific trinucleotide repeat expansion assay is available commercially in the United States and should be performed in all suspected cases of FA.

Total levels of Fe in bulk extracts were not significantly higher than normal, and the concentrations of Zn also remained in the normal range. Cu levels, however, were significantly lower in FA.

No evidence of CSF abnormality exists in patients with FA.

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Imaging Studies

Magnetic resonance imaging (MRI) is the study of choice in the evaluation of the atrophic changes seen in Friedreich ataxia (FA). MRI of the brain and spinal cord in patients with FA consistently shows atrophy of the cervical spinal cord with minimal evidence of cerebellar atrophy.

Transcranial sonography provides a quick-to-apply and inexpensive in vivo assessment of both cerebellar and noncerebellar abnormalities in FA, in particular highlighting dentate hyperechogenicity as a core feature. [8]

A mass spectroscopy assay to sensitively measure mature frataxin is being developed as per the recent 2018 FARA biomarker meeting. [58]

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Other Tests

Echocardiography reveals symmetric, concentric ventricular hypertrophy, although some have asymmetric septal hypertrophy.

Approximately 65% of patients with Friedreich ataxia (FA) have abnormal ECG findings. The most common findings are T-wave inversion, particularly in the inferior standard and lateral chest leads, and ventricular hypertrophy.

Nerve conduction velocity (NCV) study findings in FA usually are normal or display only mildly reduced velocities. Sensory nerve action potentials (SNAP) are absent in greater than 90% of patients with FA. The remaining 10% display reduced-amplitude SNAPs.

Confocal micropscopy of the skin to quantify Meissner's corpuscle, epidermal neve fiber density, and quantitative sensory testings can provide structural and physiologic markers of sensory involvement in FA. However, periodic evaluation is needed to determine whether these measures can identify changes associated with disease progression or treatment. [59]

Brainstem auditory evoked responses are typically abnormal in FA, displaying absent waves III and IV with preservation of wave I. This is suggestive of involvement of central auditory pathways.

Visual evoked potentials are abnormal in two thirds of patients with FA. Absent or delayed latency and reduced amplitude of the p100 wave are seen.

Somatosensory evoked potentials (SSEP) reveal delayed central conduction time (N13a/N20, N13b/N20), dispersed potentials at the sensory cortex, as well as abnormal central motor conduction.

Borchers et al compared clinical tests for joint position sense (JPS) and vibration sense (VS) to a test of spatial position sense (SPS). [9] The SPS test was more sensitive than JPS and VS and revealed deficits potentially earlier than clinical screening tests. Only the SPS showed a positive correlation with ataxia severity. Their results indicate that proprioceptive deficits in Friedreich ataxia start earlier and are more severe than indicated by routine standard clinical testing.

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Histologic Findings

A cross-section through the lower cervical cord clearly shows loss of myelinated fibers of the dorsal columns and the corticospinal tracts (Weil stain). Milder involvement of spinocerebellar tracts is also present. The affected tracts show compact fibrillary gliosis on hematoxylin and eosin (H&E) stain but no breakdown products or macrophages, reflecting the very slow rate of degeneration and death of fibers. The dorsal spinal ganglia show shrinkage and eventual disappearance of neurons associated with proliferation of capsular cells (H&E). The posterior roots are nearly devoid of large myelinated fibers. Within the thoracic spinal cord, degeneration and loss of cells of the Clarke column are apparent.

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Staging

Currently, there are 3 different scales that are most frequently applied: The International Cooperative Ataxia Rating Scale (ICARS), the Friedreich Ataxia Rating Scale (FARS), and the Scale for the Assessment and Rating of Ataxia (SARA). All scales have been validated and compared with regard to their testing properties. [10] )

International Cooperative Ataxia Rating Scale (World Federation of Neurology)

Posture and gait disturbances

  • Walking capacities: The patient's gait is observed during a 10-meter walking test, including a half turn, near a wall at about 1.5 meters.

    • 0 = Normal

    • 1 = Almost normal naturally, but unable to walk with feet in tandem position

    • 2 = Walking without support, but clearly abnormal and irregular

    • 3 = Walking without support, but with considerable staggering; difficulties in half turn

    • 4 = Walking with autonomous support no longer possible; the patient uses the episodic support of the wall for a 10-meter test

    • 5 = Walking possible only with 1 stick

    • 6 = Walking possible only with 2 special sticks or with a stroller

    • 7 = Walking only with accompanying person

    • 8 = Walking impossible, even with accompanying person (wheelchair)

    • Score ___

  • Gait speed: Patients who scored 1-3 on the preceding test are observed for gait speed; those who scored 4 and up on the preceding test automatically score 4 in this test.

    • 0 = Normal

    • 1 = Slightly reduced

    • 2 = Markedly reduced

    • 3 = Extremely slow

    • 4 = Walking with autonomous support no longer possible

    • Score ___

  • Standing capacities, eyes open: The patient is asked first to try to stand on one foot; if impossible, to stand with feet in tandem position; if impossible, to stand with feet together; for the natural position, the patient is asked to find a comfortable standing position.

    • 0 = Normal, able to stand on one foot for more than 10 seconds

    • 1 = Able to stand with feet together, but no longer able to stand on one foot for more than 10 seconds

    • 2 = Able to stand with feet together, but no longer able to stand with feet in tandem position

    • 3 = No longer able to stand with feet together, but able to stand in natural position without support, with no or moderate sway

    • 4 = Standing in a natural position without support, with considerable sway and considerable corrections

    • 5 = Unable to stand in natural position without strong support of one arm

    • 6 = Unable to stand at all, even with strong support of two arms

    • Score ___

  • Spread of feet in natural position without support, eyes open: The patient is asked to find a comfortable standing position, then the distance between medial malleoli is measured.

    • 0 = Normal (spread < 10 cm)

    • 1 = Slightly enlarged (spread 10-25 cm)

    • 2 = Clearly enlarged (25 cm < spread < 35 cm)

    • 3 = Severely enlarged (spread >35 cm)

    • 4 = Standing in natural position impossible

    • Score ___

  • Body sways with feet together, eyes open

    • 0 = Normal

    • 1 = Slight oscillations

    • 2 = Moderate oscillations (< 10 cm at the level of head)

    • 3 = Severe oscillations (>10 cm at the level of head), threatening the upright position

    • 4 = Immediate falling

    • Score ___

  • Body sways with feet together, eyes closed

    • 0 = Normal

    • 1 = Slight oscillations

    • 2 = Moderate oscillations (< 10 cm at the level of head)

    • 3 = Severe oscillations (>10 cm at the level of head), threatening the upright position

    • 4 = Immediate falling

    • Score ___

  • Quality of sitting position (thighs together, on a hard surface, arms folded)

    • 0 = Normal

    • 1 = With slight oscillations of the trunk

    • 2 = With moderate oscillations of the trunk and legs

    • 3 = With severe dysequilibrium

    • 4 = Impossible

    • Score ___

  • Posture and gait score (static score) ___/34

Kinetic functions

  • Knee-tibia test (decomposition of movement and intention tremor): The test is performed in the supine position so that visual control is possible; the patient is requested to raise one leg and place the heel on the opposite knee, and then slide the heel down the anterior tibial surface toward the ankle; on reaching the ankle joint, the leg is raised again in the air to a height of approximately 40 cm and the action is repeated; at least 3 movements of each limb must be performed for proper assessment.

    • 0 = Normal

    • 1 = Lowering of the heel in continuous axis but the movement is decomposed in several phases, without real jerks, or abnormally slow

    • 2 = Lowering jerkily in the axis

    • 3 = Lowering jerkily with lateral movements

    • 4 = Lowering jerkily with extremely strong lateral movements or test impossible

    • Score right ___, Score left ___

  • Action tremor in the heel-to-knee test: During the same test as the preceding one, the action tremor of the heel on the knee is observed specifically while the patient holds the heel on the knee for a few seconds before sliding it down the anterior tibial surface; visual control is required.

    • 0 = No trouble

    • 1 = Tremor stopping immediately when the heel reaches the knee

    • 2 = Tremor stopping in less than 10 seconds after reaching the knee

    • 3 = Tremor continuing for more than 10 seconds after reaching the knee

    • 4 = Uninterrupted tremor or test impossible

    • Score right ___, Score left ___

  • Finger-to-nose test (decomposition and dysmetria): The subject sits in a chair; the hand is resting on the knee before the beginning of the movement; visual control is required; 3 movements of each limb must be performed for proper assessment.

    • 0 = No trouble

    • 1 = Oscillating movement without decomposition of the movement

    • 2 = Segmented movement in 2 phases and/or moderate dysmetria in reaching nose

    • 3 = Segmented movement in more than 2 phases and/or considerate dysmetria in reaching nose

    • 4 = Dysmetria preventing the patient from reaching nose

    • Score right ___, Score left ___

  • Finger-to-nose test (intention tremor of the finger): The studied tremor is that appearing during the ballistic phase of the movement; the patient is sitting comfortably with the hand resting on his/her thigh; visual control is required; 3 movements of each limb must be performed for proper assessment.

    • 0 = No trouble

    • 1 = Simple swerve of the movement

    • 2 = Moderate tremor with estimated amplitude < 10 cm

    • 3 = Tremor with estimated amplitude between 10 and 40 cm

    • 4 = Severe tremor with estimated amplitude >40 cm

    • Score right ___, Score left ___

  • Finger-finger test (action tremor and/or instability): The sitting patient is asked to maintain his/her index fingers pointing at each other for about 10 seconds, at a distance of 1 cm, at the level of the thorax, under visual control.

    • 0 = Normal

    • 1 = Mild instability

    • 2 = Moderate oscillations of the finger with estimated amplitude < 10 cm

    • 3 = Considerable oscillations of the finger with estimated amplitude between 10 and 40 cm

    • 4 = Jerky movements >40 cm of amplitude

    • Score right ___, Score left ___

  • Pronation-supination alternating movements: The subject, comfortably sitting on a chair, is asked to raise his/her forearm vertically and to make alternating pronating and supinating movements of the hand; each hand is moved and assessed separately.

    • 0 = Normal

    • 1 = Slightly irregular and slowed

    • 2 = Clearly irregular and slowed, but without sway of the elbow

    • 3 = Extremely irregular and slowed movements, with sway of the elbow

    • 4 = Movement completely disorganized or impossible

    • Score right ___, Score left ___

  • Drawing of the Archimedes spiral on a predrawn pattern: The subject is comfortably settled in front of a table, sheet of paper being fixed to avoid artifacts; the subject is asked to perform the task without timing requirements; the same conditions of examination must be used at each examination (eg, same table, same pen); the dominant hand is examined.

    • 0 = Normal

    • 1 = Impairment and decomposition, the line quitting the pattern slightly but without hypermetric swerve

    • 2 = Line completely out of the pattern with recrossing and/or hypermetric swerves

    • 3 = Major disturbance due to hypermetria and decomposition

    • 4 = Drawing completely disorganized or impossible

    • Score ___

  • Kinetic score (limb coordination) ___/52

Speech disorders

  • Dysarthria (fluency of speech): The patient is asked to repeat several times a standard sentence, always the same, for instance, "They heard him speak on the radio last night."

    • 0 = Normal

    • 1 = Mild modification of fluency

    • 2 = Moderate modification of fluency

    • 3 = Considerably slow and dysarthric speech

    • 4 = No speech

    • Score ___

  • Dysarthria (clarity of speech)

    • 0 = Normal

    • 1 = Suggestion of slurring

    • 2 = Definite slurring, most words understandable

    • 3 = Severe slurring, speech not understandable

    • 4 = No speech

    • Score ___

  • Dysarthria score ___/8

Oculomotor disorders

  • Gaze-evoked nystagmus: The subject is asked to look laterally at the finger of the examiner; the movements assessed are mainly horizontal, but they may be oblique, rotatory, or vertical.

    • 0 = Normal

    • 1 = Transient

    • 2 = Persistent but moderate

    • 3 = Persistent and severe

    • Score ___

  • Abnormalities of the ocular pursuit: The subject is asked to follow the slow lateral movement performed by the finger of the examiner.

    • 0 = Normal

    • 1 = Slightly saccadic

    • 2 = Clearly saccadic

    • Score ___

  • Dysmetria of the saccade: Two index fingers of the examiner are placed in each temporal visual field of the patient, whose eyes are in the primary position; the patient is then asked to look laterally at the finger, on the right and on the left; the average overshoot or undershoot of the 2 sides is then estimated.

    • 0 = Absent

    • 1 = Bilateral clear overshoot or undershoot of the saccade

    • Score ___

  • Oculomotor movement score ___/6

  • Total ataxia score ___/100

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