Patients with sensory disturbances of painful and non-painful character show distinct changes in touch and/or pain sensitivity. The patterns of sensory changes were compared to those of human surrogate models of neuropathic pain to assess the underlying mechanisms. We investigated 30 consecutive in-patients with dysaesthesia of various origins (peripheral, spinal, and brainstem lesions) and 15 healthy subjects. Tactile thresholds were determined with calibrated von Frey hairs (1.1mm). Thresholds and stimulus-response functions for pricking pain were determined with a series of calibrated punctate mechanical stimulators (0.2mm). Allodynia was tested by light stroking with a brush, Q-tip, and cotton wisp. Perceptual wind-up was tested by trains of punctate stimuli at 0.2 or 1Hz. Intradermal injection of capsaicin (n=7) and A-fiber conduction blockade (n=8) served as human surrogate models for neurogenic hyperalgesia and partial nociceptive deafferentation, respectively. Patients without pain (18/30) showed a continuous distribution of threshold shifts in the dysaesthetic skin area with a low to moderate increase in pain threshold (by 1.52+/-0.45 log2 units). Patients with painful dysaesthesia presented as two separate groups (six patients each): one showing lowered pain thresholds (by -1.94+/-0.46 log2 units, hyperalgesia) and the other elevated pain thresholds (by 3.02+/-0.48 log2 units, hypoalgesia). The human surrogate model of neurogenic hyperalgesia revealed nearly identical leftward shifts in stimulus-response function for pricking pain as patients with spontaneous pain and hyperalgesia (by a factor of about 5 each). The sensory changes in the human surrogate model of deafferentation were similar to patients with hypoalgesia and spontaneous pain (rightward shift of the stimulus-response function with a decrease in slope). Perceptual wind-up did not differ between symptomatic and control areas. There was no exclusive association of any parameter obtained by quantitative sensory testing with a particular disease (of either peripheral or central origin). Our findings suggest that neuropathic pain is based on two distinct mechanisms: (I) central sensitization (neurogenic hyperalgesia; in patients with minor sensory impairment) and (II) partial nociceptive deafferentation (painful hypoalgesia; in patients with major sensory deficit). This distinction as previously postulated for postherpetic neuralgia, is obviously valid also for other conditions. Our findings emphasize the significance of a mechanism-based classification of neuropathic pain.

Our current understanding of brainstem reflex physiology comes chiefly from the classic anatomical-functional correlation studies that traced the central circuits underlying brainstem reflexes and establishing reflex abnormalities as markers for specific areas of lesion. These studies nevertheless had the disadvantage of deriving from post-mortem findings in only a few patients. We developed a voxel-based model of the human brainstem designed to import and normalize MRIs, select groups of patients with or without a given dysfunction, compare their MRIs statistically, and construct three-plane maps showing the statistical probability of lesion. Using this method, we studied 180 patients with focal brainstem infarction. All subjects underwent a dedicated MRI study of the brainstem and the whole series of brainstem tests currently used in clinical neurophysiology: early (R1) and late (R2) blink reflex, early (SP1) and late (SP2) masseter inhibitory reflex, and the jaw jerk to chin tapping. Significance levels were highest for R1, SP1 and R2 afferent abnormalities. Patients with abnormalities in all three reflexes had lesions involving the primary sensory neurons in the ventral pons, before the afferents directed to the respective reflex circuits diverge. Patients with an isolated abnormality of R1 and SP1 responses had lesions that involved the ipsilateral dorsal pons, near the fourth ventricle floor, and lay close to each other. The area with the highest probabilities of lesion for the R2-afferent abnormality was in the ipsilateral dorsal-lateral medulla at the inferior olive level. SP2 abnormalities reached a low level of significance, in the same region as R2. Only few patients had a crossed-type abnormality of SP1, SP2 or R2; that of SP1 reached significance in the median pontine tegmentum rostral to the main trigeminal nucleus. Although abnormal in 38 patients, the jaw jerk appeared to have no cluster location. Because our voxel-based model quantitatively compares lesions in patients with or without a given reflex abnormality, it minimizes the risk that the significant areas depict vascular territories rather than common spots within the territory housing the reflex circuit. By analysing statistical data for a large cohort of patients, it also identifies the most frequent lesion location for each response. The finding of multireflex abnormalities reflects damage of the primary afferent neurons; hence it provides no evidence of an intra-axial lesion. The jaw jerk, perhaps the brainstem reflex most widely used in clinical neurophysiology, had no apparent topodiagnostic value, probably because it depends strongly on peripheral variables, including dental occlusion.

Emotional facial paresis is characterized by impaired activation of face muscles with emotion but normal voluntary activation. We report seven patients with this sign. Their lesions involved the frontal lobe white matter, the striatocapsular territory, the anterolateral thalamus and insula, the posterior thalamus and operculum, and the mesial temporal lobe and insula each in one patient, and the posterior thalamus in two patients. Volitional facial paresis affects facial movements with voluntary effort, sparing activation on emotion. We report four such patients, with lesions involving the motor cortex in one and the pyramidal tract in the cerebral hemisphere in three.

During a 10 year period 24 patients with definite multiple sclerosis with isolated cranial nerve palsies were studied (third and fourth nerve: one patient each, sixth nerve: 12 patients, seventh nerve: three patients, eighth nerve: seven patients), in whom cranial nerve palsies were the presenting sign in 14 and the only clinical sign of an exacerbation in 10 patients. MRI was carried out in 20 patients and substantiated corresponding brainstem lesions in seven patients (third nerve: one patient, sixth nerve: four patients, eighth nerve: two patients). Additional abnormal findings of electro-oculography, or masseter reflex, or blink reflex, or combinations of these were found in 20 patients and interpreted in favour of a brainstem lesion at the level of the respective cranial nerve. In 11 of 14 patients with isolated cranial nerve palsies as the presenting sign of multiple sclerosis, dissemination in space was documented by MRI, and in the remaining three by evoked potentials. In patients with multiple sclerosis with isolated cranial nerve palsies, MRI is the most sensitive method of documenting dissemination in space and electrophysiological testing the most sensitive at disclosing brainstem lesions.

The masseter and medial pterygoid stretch reflexes, the masseter inhibitory reflexes, and the blink reflexes are useful diagnostic tools for evaluation of brain stem disorders. The structures mediating these reflexes are largely known. Characteristic changes of the normal response patterns due to various lesions have been described. Distinct reflex abnormalities indicate lesions at specific sites. Multireflex testing improves the accuracy with which localization can be made. A number of lesions suspected on clinical data may be confirmed by reflex findings only and not by imaging studies. Reflex testing can be utilized to demonstrate multiple lesions evoked by a single vascular event and evaluate dissemination of central nervous involvement in multiple sclerosis patients.