Chronic itch induced by thalamic deep brain stimulation: a case for a central itch centre

Background Central itch syndrome has been previously described in conditions such as stroke. The neurophysiology of central itch syndrome has been investigated in non-human primates but remains incompletely understood. Methods We report an observational study of a rare case of severe central itch following thalamic deep brain stimulation and postulate the location of the central itch centre in humans. Results The patient was a 47-year-old female, with congenital spinal malformations, multiple previous corrective spinal surgeries and a 30-year history of refractory neuropathic pain in her back and inferior limbs. Following multidisciplinary pain assessment and recommendation, she was referred for spinal cord stimulation, but the procedure failed technically due to scarring related to her multiple previous spinal surgeries. She was therefore referred to our centre and underwent bilateral deep brain stimulation (DBS) of the ventral posterolateral nucleus of the thalamus for management of her chronic pain. Four weeks after switching on the stimulation, the patient reported significant improvement in her pain but developed a full body progressive itch which was then complicated with a rash. Common causes of skin eczema were ruled out by multiple formal dermatological evaluation. A trial of unilateral “off stimulation” was performed showing improvement of the itchy rash. Standard and normalized brain atlases were used to localize the active stimulating contact within the thalamus at a location we postulate as the central itch centre. Conclusions Precise stereotactic imaging points to the lateral portion of the ventral posterolateral and posteroinferior nuclei of the thalamus as critical in the neurophysiology of itch in humans.

Dejérine-Roussy syndrome associated with unilateral thalamic glioma

Context: Déjérine-Roussy Syndrome is a rare entity that occurs after an ischemia located in the ventral posterolateral nucleus, and it is characterized by hemiplegia, superficial hemianesthesia, mild hemiataxia and astereognosis, pain on the paretic side and choreoathetosis movements. This unusual condition can be caused by haemorrhage or neoplasm. Thalamic tumors make up less than 5% of all intracranial tumors. The rare clinical presentation of a thalamic tumor is a diagnostic and therapeutic challenge for neurology and neurosurgery practice and generally requires treatment without biopsy. Case report: A 54-years-old man presented complaining of burning and tingling paraesthesias, decreased sensitivity in left dimidium, associated with decreased visual acuity in the left eye. Physical examination showed complete left hemiparesis provided grade 4-, normoreflexia with athetoid movements of the left arm and hand, painful, thermal hemihipoesthesia and epicritic touch, allodyne in the left hemibody, pressure sensitivity present globally, visual campimetry by confrontation with heteronymous hemianopia without changes in the cranial nerves. Magnetic Resonance Imaging of the Skull Base showed an oval mass, with hyposignal in T1 and hypersignal in T2 and FLAIR, with peripheral contrast uptake in the thalamus and nuclei from the right base. The patient showed good clinical-surgical evolution after surgery with Glasgow Outcome Scale 4 and modified Rankin scale 2. Anatomical Pathology confirmed low-grade glioma. Conclusions: Early diagnosis and immediate therapy can delay a fatal outcome or decrease treatment-related morbidity.

DYNAMICS OF THE IMPULSE ACTIVITY OF NEURONS IN THE VENTRAL POSTEROLATERAL NUCLEUS (VPL) OF THE RAT’S THALAMUS IN RESPONSE TO SOMATOSENSOR CORE STIMULATION IN A PARKINSON’S DISEASE MODEL

Neurodegenerative diseases are going to increase as the life expectancy is getting longer. Most patients with neurodegenerative diseases (ND) complain of pain, the origin of which remains largely unknown and requires further research. One of the reasons why the topic of pain and PD is difficult to address is that it is sometimes tough to discern whether a particular pain is due to PD or not. Chronic pain is such a common symptom among the general population, and people with PD are not immune to common problems as well. However, there are aspects of PD that may exacerbate the pain experienced from a common problem. In addition, there are particular types of pain that may be unique to people with PD. There is a frequent and more intense onset of pain in Parkinson’s disease, as the most important non-motor symptom, with a violation of both the emotional measurement of pain and the subjective perception of its intensity. In addition, various types of pain have been described in PD, mainly neuropathic or nociceptive. The presence of pain symptoms is often not taken into account in the recommendations for treatment, leaving their management at the discretion of only doctors. Studies focusing on pain frequency in such disorders suggest a high prevalence of pain in selected populations from 40% to 86% in Parkinson’s disease (PD). The methods of pain assessment vary between studies so the type of pain has been rarely reported. However, a prevalent nonneuropathic origin of pain emerged for PD. The electrophysiological investigations on 8 rats Albino lines (230±30g.) has been conducted: intacts (5 animals) and on the rotenone model of Parkinson’s disease (PD) (3 animals) has been conducted. The extracellular recording of impulse activity 229 single neurons of ventral-posterolateral nucleus (nVPL) of thalamus on high frequency stimulation of second somatosensory cortex of the brain has been produced. Analyses of relative degree frequency intensity of depressor and excitatory effects, on the bases of diagrams of average frequency of impulses, presented as disk graphs in mentioned conditions following changes of tetanic depressor and excitatory reactions, accompanied by posttetanic depressor and potentiation has been revealed. On the model of PD in both sequences, in comparison with norm, reduction in the number of neurons, responded by inhibitory poststimulus reactions has been revealed. The prestimulus frequency of nVPL neurons impulse activity, preceding to both inhibitory and excitatory sequences, in comparison with, dramatically increased turned out to be. The poststimulus frequency of impulse activity on the model of PD, accompanied by inhibitory and excitatory sequences also significantly increased turned out to be. A significant shift of frequency of pre- and poststimulus activity in pathology is a consequence of the development of excitotoxicity, that is fraught with apoptosis and dead. In conclusion, on the model of PD the excitotoxicity revealed in neurons of nVPL, leading to neurodegenerative defeat of these important antinociceptive structures of thalamus, with origin of resistant chronic pain. Marked indicates the need of protective conservation of inhibitory effects and reduced of excessive excitatory.

The right thalamic ventral posterolateral nucleus seems to be determinant for macrosomatognosia: a case report

Background Macrosomatognosiais the illusory sensation of a substantially enlarged body part. This disorder of the body schema, also called “Alice in wonderland syndrome” is still poorly understood and requires careful documentation and analysis of cases. The patient presented here is unique owing to his unusual macrosomatognosia phenomenology, but also given the unreported localization of his most significant lesion in the right thalamus that allowed consistent anatomo-clinical analysis. Case presentation This 45-years old man presented mainly with long-lasting and quasi-delusional macrosomatognosia associated to sensory deficits, both involving the left upper-body, in the context of a right thalamic ischemic lesion most presumably located in the ventral posterolateral nucleus. Fine-grained probabilistic and deterministic tractography revealed the most eloquent targets of the lesion projections to be the ipsilateral precuneus, superior parietal lobule,but also the right primary somatosensory cortex and, to a lesser extent, the right primary motor cortex. Under stationary neurorehabilitation, the patient slowly improved his symptoms and could be discharged back home and, later on, partially return to work. Conclusion We discuss deficient neural processing and integration of sensory inputs within the right ventral posterolateral nucleus lesion as possible mechanisms underlying macrosomatognosia in light of observed anatomo-clinical correlations. On the other hand, difficulty to classify this unique constellation of Alice in wonderland syndrome calls for an alternative taxonomy of cognitive and psychic aspects of illusory body-size perceptions.

Stereotactic radiofrequency ventral posterolateral thalamotomy for cancer pain

Palliative neuroablative procedures are often performed for medication-refractory cancer pain. A 57-year-old female with lung carcinoma and metastases to the brachial plexus and cervical spine with severe neuropathic pain affecting the right upper limb was referred to the authors’ functional neurosurgery service. This video shows her treatment with an awake stereotactic radiofrequency thalamotomy targeting the left ventral posterolateral nucleus. Postoperatively, she experienced immediate and complete resolution of the pain. Palliative radiofrequency thalamotomy can be a viable and effective procedure for somatotopically distributed regional cancer pain.The video can be found here: https://youtu.be/jykYWXTP3c4

A New Rat Model of Thalamic Pain Produced by Administration of Cobra Venom to the Unilateral Ventral Posterolateral Nucleus

Background: Thalamic pain is a neuropathic pain syndrome that occurs as a result of thalamic damage. It is difficult to develop therapeutic interventions for thalamic pain because its mechanism is unclear. To better understand the pathophysiological basis of thalamic pain, we developed and characterized a new rat model of thalamic pain using a technique of microinjecting cobra venom into the ventral posterolateral nucleus (VPL) of the thalamus. Objectives: This study will establish a new thalamic pain rat model produced by administration of cobra venom to the unilateral ventral posterolateral nucleus. Study Design: This study used an experimental design in rats. Setting: The research took place in the laboratory at the Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine. Methods: Male Sprague-Dawley rats were subjected to the administration of cobra venom or saline into the left VPL. The development of mechanical hyperalgesia and changes in pain-related behaviors and motor function were measured after intrathalamic cobra venom microinjection using the von Frey test, video recording, and cylinder test, respectively. On postoperative days 7 to 35, both electroacupuncture and pregabalin (PGB) were administered to verify that the model reproduced the findings in humans. Moreover, the organizational and structural alterations of the thalamus were examined via transmission electron microscopy (TEM). Results: The threshold for mechanical stimuli in the left facial skin was significantly decreased on day 3 after thalamic pain modeling as compared with pre-venom treatment. Furthermore, the ultrastructural alterations of neurons such as indented neuronal nuclei, damaged mitochondria and endoplasmic reticulum, and dissolved surrounding tissues were observed under TEM. Moreover, electroacupuncture treatment ameliorated mechanical hyperalgesia, pain-like behaviors, and motor dysfunction, as well as restore normal structures of neurons in the thalamic pain rat model. However, no such beneficial effects were noted when PGB was administered. Limitations: The pathophysiological features were different from the present model and the patients in clinical practice (in most cases strokes, either ischemic or hemorrhagic). Conclusion: The cobra venom model may provide a reasonable model for investigating the mechanism of thalamic pain and for testing therapies targeting recovery and pain after thalamic lesions.

Dejerine-Roussy syndrome

On June 7, 1906, Jules Dejerine (1849–1917) and Gustave Roussy (1874–1948) presented to the Société de Neurologie de Paris the first description of the thalamic syndrome with serial-section microscopic images. They also provided the first account of central poststroke pain (CPSP). They suggested that pain is one of the primary symptoms of the syndrome, although one of their own patients (“Hud”) did not have pain. Several contemporary studies have highlighted the involvement of the anterior part of the pulvinar (PuA) in patients with CPSP of thalamic origin. Two historical observations (cases Jos and Hud) are reviewed here using the Morel nuclei staining atlas (2007). Dejerine and Roussy proposed the “irritative theory” to explain CPSP of thalamic origin and, in line with the most recent literature, they invoked the involvement of the PuA. When matching images for the Jos and Hud cases with the Morel atlas, it appears that the lesions involved what Dejerine then termed the noyau externe; that is, the ventral posterolateral nucleus and the PuA. In the Jos case, the lesion extended medially to what Dejerine termed the noyau médian de Luys; that is, the central medial–parafascicular nuclei, whereas in the Hud case the lesion extended more inferiorly. From the finding in the Hud case, one can hypothesize that impairment of the PuA alone does not assure pain. The work of Dejerine and Roussy, based on clinico-anatomical correlations, remains relevant to this day.

Feed-forward information and zero-lag synchronization in the sensory thalamocortical circuit are modulated during stimulus perception

The direction of functional information flow in the sensory thalamocortical circuit may play a role in stimulus perception, but, surprisingly, this process is poorly understood. We addressed this problem by evaluating a directional information measure between simultaneously recorded neurons from somatosensory thalamus (ventral posterolateral nucleus, VPL) and somatosensory cortex (S1) sharing the same cutaneous receptive field while monkeys judged the presence or absence of a tactile stimulus. During stimulus presence, feed-forward information (VPL → S1) increased as a function of the stimulus amplitude, while pure feed-back information (S1 → VPL) was unaffected. In parallel, zero-lag interaction emerged with increasing stimulus amplitude, reflecting externally driven thalamocortical synchronization during stimulus processing. Furthermore, VPL → S1 information decreased during error trials. Also, VPL → S1 and zero-lag interaction decreased when monkeys were not required to report the stimulus presence. These findings provide evidence that both the direction of information flow and the instant synchronization in the sensory thalamocortical circuit play a role in stimulus perception.