Late-onset neurological symptoms in thalidomide-exposed subjects: a study of an Australasian cohort.

BACKGROUND AND PURPOSE: Thalidomide was marketed for the treatment of morning sickness and resulted in foetal death and physical deformities. The exact mechanism of action of thalidomide in its teratogenicity is still actively debated in the literature. METHODS: This study reviewed 16 of the confirmed Australasian victims of in utero exposure to thalidomide who now presented with new-onset neurological symptoms in the fourth and fifth decades. RESULTS: Clinical neurological examination and neurophysiological investigations revealed that new symptoms were due in part to compressive neuropathies, often exacerbated by the adaptations made to accommodate the disability and poor mobility arising from the limb deformities. Other subjects were found to have musculoskeletal symptoms due to compensatory postures employed to perform tasks of daily living. CONCLUSIONS: The study provides no evidence of ongoing loss of neurons or late reactivated neural degeneration and no evidence of a generalized peripheral neuropathy. Rather, the development of new symptoms in subjects can be explained by compressive neuropathies and compensatory postures employed to perform tasks of daily living.

A comparison of the excitability of motor axons innervating the APB and ADM muscles.

OBJECTIVE: Threshold tracking allows the non-invasive assessment of axonal excitability. This study aimed to determine whether axonal excitability of the motor axons of the median nerve (to APB) and ulnar nerve (to ADM) to the small muscles of the hands is sufficiently similar to be interchangeable; confirm the feasibility and reproducibility of ulnar studies and obtain control data for a young population for this site of stimulation. METHODS: Twenty normal subjects between the ages of 23-43 were studied using the TRONDF protocol of QTRACS, (©Prof Hugh Bostock, London). The median and ulnar nerves were stimulated at the wrist and the compound muscle action potentials were recorded from abductor pollicis brevis and abductor digiti minimi, respectively. Repeat studies were performed in four subjects to confirm reproducibility of the recordings. RESULTS: Stimulus intensity was greater and strength duration time constant was longer for the median nerve. Threshold electrotonus showed there was a greater change in threshold in the hyperpolarising direction for the median nerve compared with the ulnar nerve. There was however little difference in the recovery cycle and current threshold relationship. CONCLUSIONS: Although recovery cycles and the current thresholds are similar for APB and ADM, there are definite differences in stimulus threshold, SDTC and threshold electrotonus which question the interchangeability of studies for these two sites. SIGNIFICANCE: This study demonstrates reproducibility of motor axonal excitability studies of the ulnar nerve at the wrist, provides young control data for this site of stimulation and suggests that although certain excitability indices are similar for the median nerve to APB and ulnar nerve to ADM there are definite differences making the interchangeability of the data questionable.

Axonal excitability in the forearm: normal data and differences along the median nerve.

OBJECTIVE: This study was designed to validate excitability studies of motor axons in the median nerve at the elbow, innervating forearm muscles (flexor carpi radialis, FCR) and collect normal data for this stimulation site. The differences in measures of excitability due to different sites of stimulation or a different test muscle group was also determined. METHODS: The median nerve was stimulated at the elbow and excitability studies were recorded from FCR and abductor policis brevis, APB. Further studies stimulated the median nerve at the wrist and recorded from APB. The study was performed using the TRONDCM protocol of QTRACS. RESULTS: Stimulus-response curves for FCR were significantly less steep than those for APB. There was "fanning in" of threshold electrotonus and less accommodation to hyperpolarising pulses for FCR axons. FCR studies showed significantly less supernormality. CONCLUSION: There are differences in axonal excitability along a single nerve in the human upper limb, even when the nerve is stimulated at one site and recordings are made from different muscles. SIGNIFICANCE: Normal values for one muscle group cannot be assumed to be the same for a different muscle group. The findings for FCR axons will be of value in studies on patients with central nervous system disorders.

Changes in measures of motor axon excitability with age.

OBJECTIVE: Threshold tracking is a novel technique that permits examination of the excitability of human axons in vivo. Protocols have been validated for sensory and motor axons, but there are limited data on the changes in the excitability of motor axons with age. This study aimed to determine such changes from the third to the eighth decades. METHODS: Sixty healthy subjects aged 22-79, 10 per decade, were studied using the TRONDXM4 protocol of the QTRAC threshold-tracking program to assess motor axon function. The median nerve was stimulated at the wrist and the compound muscle action potential was recorded from the thenar muscles. RESULTS: There was an increase in threshold in elderly subjects, associated with a decrease in slope of the stimulus-response curves. Strength-duration time constant and threshold electrotonus to depolarising and hyperpolarising currents of up to 40% did not change significantly with aging. The current-threshold relationship was similar across all decades for subthreshold depolarising currents, but the slope of the current-threshold relationship was significantly steeper the older the subjects for hyperpolarising currents, particularly those greater than 40% of threshold. There was also a significant decrease in supernormality in the recovery cycle with increasing age. CONCLUSIONS: The threshold of axons increases with age and the extent of supernormality decreases. There may also be greater inward rectification in motor axons, perhaps due to greater activity of I(H), the hyperpolarisation-activated conductance, though this is only significant with hyperpolarising currents greater than 40% of the threshold current. SIGNIFICANCE: Many indices of axonal excitability, such as strength-duration time constant, the relative refractory period, late subnormality, threshold electrotonus and the depolarising side of the current-threshold relationship, do not change significantly with age. For other indices, age-related changes may be due to a combination of non-neural factors that alter current access to the node of Ranvier, changes in the axon and its myelination and, possibly, changes in channel activity and/or changes in extracellular [K(+)](o).

Movement related potentials in acutely induced weakness and stroke.

Weakness is a common symptom of neurological illness, and recovery may occur via restorative or compensatory mechanisms. Functional imaging studies have shown varied patterns of activity in motor areas following recovery from stroke. Movement related potentials (MRP) reflect the activity in primary and non-primary motor areas. We recorded MRPs in association with index finger abduction in six normal volunteers before and after induced weakness of a hand muscle and in six stroke patients with subcortical lesions and weakness affecting the arm. In both groups of subjects the greatest change was observed in the motor potential component of the MRP. On average, the motor potential had its greatest amplitude and duration at the time of the greatest weakness and became smaller with recovery. In artificially-induced weakness, the MRP had an earlier onset latency (P=0.042) and a greater early BP component (P=0.05) for the weakened finger. For the stroke subjects overall, the peak and NS' amplitudes were largest for the initial study and declined thereafter. Similar but smaller changes were present for movements of the clinically unaffected side. The increased motor potential is therefore consistent with increased activity in the motor cortex, and this may occur as compensation for weakness in both normals and after stroke.

Galvanic evoked vestibulospinal and vestibulocollic reflexes in stroke.

OBJECTIVE: Following stroke, the startle reflex, mediated via the reticulospinal tract, is often facilitated. Vestibulospinal reflexes are another bulbospinal reflex, abnormalities of which may contribute to impaired body posture and stance following stroke. We recorded galvanic evoked vestibulospinal and vestibulocollic reflexes to assess whether these showed similar changes to those for startle following stroke affecting the pons and above. METHODS: Twenty-four stroke subjects (aged 40-82) were studied in the vestibulospinal part of the study, 21 stroke subjects (aged 40-81 years) were studied in the vestibulocollic part, including 18 studied in both. Transmastoid galvanic (DC) current was used to stimulate the vestibular nerve. Vestibulocollic responses were recorded from the sternocleidomastoid muscles and vestibulospinal responses from over soleus in standing subjects. RESULTS: Vestibulocollic reflex amplitudes and latencies showed no significant differences between the two sides. Similarly short latency (SL) and medium latency (ML) vestibulospinal reflexes did not differ significantly in frequency, latency or amplitude between the affected and unaffected legs. CONCLUSIONS: Vestibular reflexes are not facilitated by stroke at or above the pontine level. The exaggeration of startle by stroke may be specific to this reflex.

The acoustic startle reflex in ischemic stroke.

The authors recorded the acoustic startle response in 32 patients with stroke, 6 patients with incomplete cervical cord lesions, and 26 controls. Increased startle occurred in about one quarter of both stroke and spinal cord injury patients. The response in biceps demonstrated the greatest deviation from normal, with less marked changes in tibialis anterior. Increased startle in spinal cord injury suggests that changes at the segmental level may contribute. Symptomatic increased startle occurred only in pontine lesions.

Movement-related potentials associated with self-paced, cued and imagined arm movements.

Self-paced movements, movement to a cue and imagined movement have all been reported to be preceded by a prolonged negativity on averaged electroencephalograph (EEG) recordings. Considerable evidence supports an important contribution from the supplementary motor area (SMA) to this potential and all three types of movement have been shown to be associated with SMA activation. This study was designed to compare the premovement component of these movement-related potentials (MRPs) in a group of subjects who performed each of these three types of movement. In addition, in view of the greater SMA activation in association with proximal arm movements, we studied movements at multiple joints in the right arm. All the potentials were largest at Cz. Self-paced movements were preceded by a negativity (mean onset 1.2 s prior to electromyographic activity) with two distinct phases - an early slow increase (early BP, Bereitschaftspotential) and a later, steeper phase (NS', negative slope). Proximal movements were associated with a larger peak amplitude (mean peak amplitude for shoulder 11.6 micro V, finger movement 9.0 micro V at Cz, n=14) due to a bigger NS' phase. Movements to a regular cue, but not to a randomly timed cue, were also preceded by a long duration negativity, but the NS' phase began earlier and was less distinct than for self-paced movements (mean peak amplitude for shoulder movement 9.1 micro V, finger 8.2 micro V at Cz, n=12). Imagining the movements to a regular cue was associated with a slow negativity, with no clear NS' phase (mean peak amplitude for shoulder movement 6.5 micro V, finger 6.2 micro V at Cz). Our results indicate that the MRPs prior to the three types of movement have distinct characteristics, most notably for the NS' phase. The MRP associated with movement to a regular cue may be analogous to the S2-related negativity of the contingent negative variation (CNV). We discuss the findings in the light of current evidence from functional imaging as to the cortical areas activated in similar movements.

Perceptions and knowledge about the acquired immunodeficiency syndrome among students in university residences.

Using an anonymous questionnaire to obtain baseline data on sexual behaviour and knowledge of the acquired immunodeficiency syndrome (AIDS) among students in university residences, the following information was obtained: Knowledge of AIDS was found to be high, although misconceptions regarding transmission of the virus were prevalent. Mosquito bites (15%) and the donating of blood (31%) were incorrectly identified as methods of transmission of the virus. Deep kissing was recognised by only 27% of the students as a possible method of transmission while 22% and 13% of the students, respectively, failed to identify the sharing of razor blades and blood transfusions as possible means of contracting HIV infection. The students' knowledge had not greatly affected sexual behaviour. Two-thirds of the respondents had previously had sexual contact; 38% were sexually active at the time of the study, and of these 74% had engaged in unprotected intercourse with casual partners in the previous 6 months. There was a negative attitude towards condom use and over 80% of sexually active students did not perceive themselves to be at risk of contracting AIDS. Campus Health (82%), State health services (51%), and public advertisements (60%) were preferred sources of AIDS information. Newspapers/magazines (80%) and leaflets (69%) were identified as the preferred media. In reality, significantly fewer students obtained their information from Campus Health (15%; P less than 0.05), State health services (19%, P less than 0.05) and leaflets (44%; P less than 0.05). It can be concluded that education programmes should be developed by credible organisations to ensure that an awareness of AIDS results in appropriate sexual behaviour.