Isolated truncal contrapulsion as a rare presentation of acute thalamic infarct.

Infarcts involving the thalamus can yield many deficits, including sensory syndromes, altered consciousness, and cognitive disturbances, depending on the thalamic vascular territory involved. Isolated truncal contrapulsion due to pure thalamic infarct has been rarely reported. Truncal lateropulsion is a compelling sensation of being pulled toward one side that cannot be explained by weakness or limb ataxia. It is commonly reported in lateral medullary infarcts. It may occur with lesions that involve the peripheral vestibular system, brainstem, cerebellum, basal ganglia, ponto-mesencephalic, and thalamic lesions. We hereby report a 64-year-old woman who presented with truncal contrapulsion as the sole manifestation of an acute right lateral thalamic infarct.

Passive accessory joint mobilization in the multimodal management of chronic dysesthesia following thalamic stroke.

Study design: Case Report. Purpose: Stroke is the most common cause of long-term disability. Dysesthesia, an unpleasant sensory disturbance, is common following thalamic stroke and evidence-based interventions for this impairment are limited. The purpose of this case report was to describe a decrease in dysesthesia following manual therapy intervention in a patient with history of right lacunar thalamic stroke. Case description: A 66-year-old female presented with tingling and dysesthesia in left hemisensory distribution including left trunk and upper/lower extremities, limiting function. Decreased left shoulder active range of motion, positive sensory symptoms but no sensory loss in light touch was found. She denied pain and moderate shoulder muscular weakness was demonstrated. Laterality testing revealed right/left limb discrimination deficits and neglect-like symptoms were reported. Passive accessory joint motion assessment of glenohumeral and thoracic spine revealed hypomobility and provoked dysesthesia. Interventions included passive oscillatory joint mobilization of glenohumeral joint, thoracic spine, ribs and shoulder strengthening. Results: After six sessions, shoulder function, active range of motion, strength improved and dysesthesia decreased. Global Rating of Change Scale was +5 and QuickDASH score decreased from 45% to 22% disability. Laterality testing was unchanged. Conclusion: Manual therapy may be a beneficial intervention in management of thalamic stroke-related dysesthesia. Implications for Rehabilitation While pain is common following thalamic stroke, patients may present with chronic paresthesia or dysesthesia, often in a hemisensory distribution. Passive movement may promote inhibition of hyperexcitable cortical pathways, which may diminish aberrant sensations. Passive oscillatory manual therapy may be an effective way to treat sensory disturbances such as paresthesias or dysesthesia.

Thalamic Diaschisis in Acute Ischemic Stroke: Occurrence, Perfusion Characteristics, and Impact on Outcome.

BACKGROUND AND PURPOSE: Ipsilateral thalamic diaschisis (ITD) describes the reduction of thalamic function, metabolism, and perfusion resulting from a distant lesion of the ipsilateral hemisphere. Our aim was to evaluate the perfusion characteristics and clinical impact of ITD in acute middle cerebral artery stroke, which does not directly affect the thalamus. METHODS: One hundred twenty-four patients with middle cerebral artery infarction were selected from a prospectively acquired cohort of 1644 patients who underwent multiparametric computed tomography (CT), including CT perfusion for suspected stroke. Two blinded readers evaluated the occurrence of ITD, defined as ipsilateral thalamic hypoperfusion present on ≥2 CT perfusion maps. Perfusion alterations were defined according to the Alberta Stroke Program Early CT Score regions. Final infarction volume and subacute complications were assessed on follow-up imaging. Clinical outcome was quantified using the modified Rankin Scale. Multivariable linear and ordinal logistic regression analysis were applied to identify independent associations. RESULTS: ITD was present in 25/124 subjects (20.2%, ITD+). In ITD+ subjects, perfusion of the caudate nucleus, internal capsule, and lentiform nucleus was more frequently affected than in ITD- patients (each with P<0.001). In the ITD+ group, larger cerebral blood flow (P=0.002) and cerebral blood volume (P<0.001) deficit volumes, as well as smaller cerebral blood flow-cerebral blood volume mismatch (P=0.021) were observed. There was no independent association of ITD with final infarction volume or clinical outcome at discharge in treatment subgroups (each with P>0.05). ITD had no influence on the development of subacute stroke complications. CONCLUSIONS: ITD in the form of thalamic hypoperfusion is a frequent CT perfusion finding in the acute phase in middle cerebral artery stroke patients with marked involvement of subcortical areas. ITD does not result in thalamic infarction and had no independent impact on patient outcome. Notably, ITD was misclassified as part of the ischemic core by automated software, which might affect patient selection in CT perfusion-based trials.

The Posterior Limb of the Internal Capsule as the Subcortical Transitional Zone of the Anterior and Posterior Circulations: Insights from Human 7T MRI.

BACKGROUND: In patients with cerebral infarction, identifying the distribution of infarction and the relevant artery is essential for ascertaining the underlying vascular pathophysiological mechanisms and preventing subsequent stroke. However, visualization of the basal perforating arteries (BPAs) has had limited success, and simultaneous viewing of background anatomical structures has only rarely been attempted in living human brains. Our study aimed at identifying the BPAs with 7T MRI and evaluating their distribution in the subcortical structures, thereby showing the clinical significance of the technique. METHODS: Twenty healthy subjects and 1 patient with cerebral infarction involving the posterior limb of the internal capsule (ICpost) and thalamus underwent 3-dimensional fast spoiled gradient-echo sequence as time-of-flight magnetic resonance angiography (MRA) at 7T with a submillimeter resolution. The MRA was modified to detect inflow signals from BPAs, while preserving the background anatomical signals. BPA stems and branches in the subcortical structures and their origins were identified on images, using partial maximum intensity projection in 3 dimensions. RESULTS: A branch of the left posterior cerebral artery (PCA) in the patient ran through both the infarcted thalamus and ICpost and was clearly the relevant artery. In 40 intact hemispheres in healthy subjects, 571 stems and 1,421 branches of BPAs were detected in the subcortical structures. No significant differences in the numbers of stems and branches were observed between the intact hemispheres. The numbers deviated even less across subjects. The distribution analysis showed that the subcortical structures of the telencephalon, such as the caudate nucleus, anterior limb of the internal capsule, and lenticular nucleus, were predominantly supplied by BPAs from the anterior circulation. In contrast, the thalamus, belonging to the diencephalon, was mostly fed by BPAs from the posterior circulation. However, compared with other subcortical structures, the ICpost, which marks the anatomical boundary between the telencephalon and the diencephalon, was supplied by BPAs with significantly more diverse origins. These BPAs originated from the internal carotid artery (23.1%), middle cerebral artery (38.5%), PCA (17.3%), and the posterior communicating artery (21.1%). CONCLUSIONS: The modified MRI method allowed the detection of the relevant BPA within the infarcted area in the stroke survivor as well as the BPAs in the subcortical structures of living human brains. Based on in vivo BPA distribution analyses, the ICpost is the transitional zone of the anterior and posterior cerebral circulations.

Dynamic changes in sleep-related breathing abnormalities in bilateral paramedian mesencephalon and thalamus stroke: a follow-up case study.

BACKGROUND: Bilateral paramedian thalamic stroke is characterized by hypersomnia, vertical gaze palsy, amnestic alteration, and apathic state. Combined lesion of the paramedian thalamus and mesencephalon bilaterally is extremely rare. Little is known about the breathing disturbances of the particular region due to the lesion. The following describes the specific case of a woman, age 62, with bilateral paramedian thalamic and mesencephalic stroke. Initially, the patient's complaints exhibited altered vigilance and vertical gaze palsy. Notably, following the acute phase, fluctuating hypersomnia was detected. The MRI (brain) revealed an ischemic lesion in the medial part of the mesencephalon and paramedian thalamus, bilaterally. AIMS: The aim of the present study is to elucidate the involvement and characteristics of sleep-related breathing abnormalities in the clinical manifestation of the combined paramedian thalamic and mesencephalic stroke. METHODS: Polysomnographic recordings were accomplished seven times with 1-week interval between the consecutive recordings, toward investigating the early changes of sleep and sleep-related breathing abnormalities. RESULTS: Sleep structure examination featured a decrease in N3 and REM ratio and an increase in N1 and N2 ratio with minimal improvement during the recovery period. In contrast, significant changes were found in the breathing pattern: the initial central apnea dominance was followed by obstructive apneas with a gradual decrease of the total pathological respiratory events. CONCLUSION: In addition to the structural abnormality of the sleep regulating network, sleep-disordered breathing is another possible cause of hypersomnia in patients afflicted with the present localization of the lesion.

[Neuroanatomical Networks Supporting Memory and Their Relation to Amnesia; a View from the Thalamus].

The anterior and mediodorsal thalamic nuclei form neuroanatomical networks supporting memory along with the mammillary body, medial temporal structures, prefrontal cortices and posterior cingulate cortex. In this review article, we discuss human diencephalic amnesic syndromes, including Wernicke-Korsakoff syndrome and amnesia associated with thalamic infarcts, and animal neuropsychological studies from a neuroanatomical network perspective. In addition, we suggest future research directions for understanding the functional roles of the anterior and mediodorsal thalamic nuclei in memory function based on findings from recent animal studies.

Repeated head trauma is associated with smaller thalamic volumes and slower processing speed: the Professional Fighters' Brain Health Study.

OBJECTIVES: Cumulative head trauma may alter brain structure and function. We explored the relationship between exposure variables, cognition and MRI brain structural measures in a cohort of professional combatants. METHODS: 224 fighters (131 mixed martial arts fighters and 93 boxers) participating in the Professional Fighters Brain Health Study, a longitudinal cohort study of licensed professional combatants, were recruited, as were 22 controls. Each participant underwent computerised cognitive testing and volumetric brain MRI. Fighting history including years of fighting and fights per year was obtained from self-report and published records. Statistical analyses of the baseline evaluations were applied cross-sectionally to determine the relationship between fight exposure variables and volumes of the hippocampus, amygdala, thalamus, caudate, putamen. Moreover, the relationship between exposure and brain volumes with cognitive function was assessed. RESULTS: Increasing exposure to repetitive head trauma measured by number of professional fights, years of fighting, or a Fight Exposure Score (FES) was associated with lower brain volumes, particularly the thalamus and caudate. In addition, speed of processing decreased with decreased thalamic volumes and with increasing fight exposure. Higher scores on a FES used to reflect exposure to repetitive head trauma were associated with greater likelihood of having cognitive impairment. CONCLUSIONS: Greater exposure to repetitive head trauma is associated with lower brain volumes and lower processing speed in active professional fighters.

Barriers to investigator-initiated deep brain stimulation and device research.

The success of device-based research in the clinical neurosciences has overshadowed a critical and emerging problem in the biomedical research environment in the United States. Neuroprosthetic devices, such as deep brain stimulation (DBS), have been shown in humans to be promising technologies for scientific exploration of neural pathways and as powerful treatments. Large device companies have, over the past several decades, funded and developed major research programs. However, both the structure of clinical trial funding and the current regulation of device research threaten investigator-initiated efforts in neurologic disorders. The current atmosphere dissuades clinical investigators from pursuing formal and prospective research with novel devices or novel indications. We review our experience in conducting a federally funded, investigator-initiated, device-based clinical trial that utilized DBS for thalamic pain syndrome. We also explore barriers that clinical investigators face in conducting device-based clinical trials, particularly in early-stage studies or small disease populations. We discuss 5 specific areas for potential reform and integration: (1) alternative pathways for device approval; (2) eliminating right of reference requirements; (3) combining federal grant awards with regulatory approval; (4) consolidation of oversight for human subjects research; and (5) private insurance coverage for clinical trials. Careful reformulation of regulatory policy and funding mechanisms is critical for expanding investigator-initiated device research, which has great potential to benefit science, industry, and, most importantly, patients.

Connectivity-based parcellation of the thalamus explains specific cognitive and behavioural symptoms in patients with bilateral thalamic infarct.

A novel approach based on diffusion tractography was used here to characterise the cortico-thalamic connectivity in two patients, both presenting with an isolated bilateral infarct in the thalamus, but exhibiting partially different cognitive and behavioural profiles. Both patients (G.P. and R.F.) had a pervasive deficit in episodic memory, but only one of them (R.F.) suffered also from a dysexecutive syndrome. Both patients had an MRI scan at 3T, including a T1-weighted volume. Their lesions were manually segmented. T1-volumes were normalised to standard space, and the same transformations were applied to the lesion masks. Nineteen healthy controls underwent a diffusion-tensor imaging (DTI) scan. Their DTI data were normalised to standard space and averaged. An atlas of Brodmann areas was used to parcellate the prefrontal cortex. Probabilistic tractography was used to assess the probability of connection between each voxel of the thalamus and a set of prefrontal areas. The resulting map of corticothalamic connections was superimposed onto the patients' lesion masks, to assess whether the location of the thalamic lesions in R.F. (but not in G. P.) implied connections with prefrontal areas involved in dysexecutive syndromes. In G.P., the lesion fell within areas of the thalamus poorly connected with prefrontal areas, showing only a modest probability of connection with the anterior cingulate cortex (ACC). Conversely, R.F.'s lesion fell within thalamic areas extensively connected with the ACC bilaterally, with the right dorsolateral prefrontal cortex, and with the left supplementary motor area. Despite a similar, bilateral involvement of the thalamus, the use of connectivity-based segmentation clarified that R.F.'s lesions only were located within nuclei highly connected with the prefrontal cortical areas, thus explaining the patient's frontal syndrome. This study confirms that DTI tractography is a useful tool to examine in vivo the effect of focal lesions on interconnectivity brain patterns.

'Distorteidolias' - fantastic perceptive distortion. A new, pure dorsomedial thalamic syndrome.

The role of the thalamus in the pathogenesis of the visual and auditory hallucinations has been reported under the name of peduncular hallucinosis, usually with coexisting midbrain involvement. These hallucinations typically take the form of dreamy de novo productions (phanteidolias), less often that of transformations of perceptions into new items (such as seeing faces in clouds) called pareidolias. However, hallucinations taking the form of a complex distortion of perception is a different phenomenon, which to our knowledge has not been reported. We studied 2 patients with complex, 'fantastic', perceptive distortion involving the visual and auditory systems after thalamic stroke limited to the region of the dorsomedial nucleus, sparing the intralaminar nuclei and the midbrain (explaining the lack of disorders of consciousness and confusional state). Our patients reported the modification of usual stimuli (face, body, voices) into unreal, fantastically distorted perceptions (monstrous change of shapes or sounds without appearance of new items). While the exact mechanism leading to such perceptive distortions remains unknown, a release phenomenon due to damage to the dorsomedial thalamus (probably affecting cholinergic system) responsible for a disinhibition of cortical function involved in familiarity of perception seems likely. We suggest that these hallucinations should be called 'distorteidolias'.

Minimally invasive procedures reduced the damages to motor function in patients with thalamic hematoma: observed by motor evoked potential and diffusion tensor imaging.

BACKGROUND: The purpose of this study was to observe changes in motor function using diffusion tensor imaging (DTI) and motor-evoked potential (MEP) in patients with thalamic hematoma treated by minimally invasive procedures. METHODS: Forty-three patients with thalamic hematoma were randomized to either a minimally invasive group (MI group) or a medical treatment group (MT group). The patients in the MI group underwent whole-brain DTI and MEP measurements both before and 2 weeks after the thalamic hematoma was evacuated by minimally invasive procedures. The fractional anisotropy (FA) values of the corticospinal tract (CST) in the internal capsule and MEP ipsilateral to the hematoma side and the contralateral side were determined and then compared with the MT group. RESULTS: DTI showed that fibers in the internal capsule ipsilateral to the hematoma decreased either in number or were interrupted because of hematoma-induced damages, and in both groups, the CST FA values on admission were significantly lower (0.428 ± 0.032 and 0.415 ± 0.048 for the MI and MT groups, respectively) than the control values. Two weeks after the hematoma was evacuated, the number of fibers and the FA values of the CST in the internal capsule had both increased significantly relative to the values on admission. MEP was recorded simultaneously in all patients who were treated with minimally invasive procedures, and the latency of MEP decreased compared with the MT group. As FA values of the CST in internal capsule increased and MEP appeared with its latency decreased, the modified National Institutes of Health Stroke Scale score decreased after the surgery. CONCLUSIONS: Minimally invasive procedures for thalamic hematoma evacuation could effectively reduce the degree of injury to the function as observed by a combination of DTI and MEP measurements.

Conserved functional connectivity but impaired effective connectivity of thalamocortical circuitry in schizophrenia.

Schizophrenia is a severe mental illness with neurobiological bases that remain elusive. One hypothesis emphasizes disordered thalamic function. We previously used concurrent single pulse transcranial magnetic stimulation (spTMS) and functional magnetic resonance imaging (fMRI) to show that individuals with schizophrenia have a decreased spTMS-evoked response in the thalamus, and decreased effective connectivity between thalamus and insula and thalamus and superior frontal gyrus. To better understand the factors that may accompany or account for these findings, we investigated, in the same participants, resting state functional connectivity, white matter structural connectivity, and grey matter integrity. Patients with schizophrenia did not differ from healthy control subjects in resting state functional- or white matter structural connectivity, although they did show decreased measures of grey matter integrity in the insula. However, in this region, the spTMS-evoked response did not differ between groups. In a region of the thalamus that also had grey matter intensity abnormalities, although not at a level that survived correction for multiple comparisons, the spTMS-evoked response in patients was deficient. These results suggest that measures of structure and function are not necessarily complementary. Further, given its sensitivity for identifying deficits not evident with traditional imaging methods, these results highlight the utility of spTMS-fMRI, a method that directly and causally probes effective connectivity, as a tool for studying brain-based disorders.

Improved dexterity after chronic electrical stimulation of the motor cortex for central pain: a special relevance for thalamic syndrome.

OBJECTIVES: To demonstrate that motor cortex stimulation (MCS) could improve motor function in patients with neuropathic pain. METHODS: In this prospective clinical study of 38 patients referred for MCS as treatment for their neuropathic pain, we collected any declaration of improvement in motor performance that could be attributed to MCS. RESULTS: Ten patients (26%) declared a benefit in their motor function. Eight presented objective evidence of recovered dexterity for rapid alternating movements. A minor proportion had improvement in dystonic posture (n = 2), but none had detectable increased motor strength or tonus changes. Overall, 73% of the patients with limb ataxia declared a benefit after MCS. In 6 out of 10 patients (60%), the anatomic lesion responsible for pain was restricted to the lateral aspect of the thalamus. All of them had either clinical or electrophysiological evidence of lemniscal dysfunction (proprioceptive ataxia). No correlation was found between the scores of pain relief and the modification of motor status. The correlation between thalamic lesions and benefits in motor performance was significant (Fisher's exact test, two-tailed, p = 0.0017). CONCLUSIONS: Up to 26% of patients estimated that MCS improved their motor outcome through recovered dexterity and in cases of lateral thalamic lesions.

Insights gained into pain processing from patients with focal brain lesions.

The recognition that dissociated sensory loss affecting selectively pain and temperature results from lesions of the operculo-insular cortex is due to Biemond in 1956. This contrasted with the prevailing view that the sensory aspects of pain did not imply regions above the thalamus. Anatomical data in non-human primates, as well as electrophysiology and functional imaging in humans have now abundantly demonstrated that the opercular-insular region is the main cortical target of the spinothalamic system, and a vast number of reports have confirmed the relation between lesions in this region and the development of dissociated sensory symptoms and central neuropathic pain. Operculo-insular pain (parasylvian pain) is a distinct entity that can be clinically suspected and objectively diagnosed with combined radiological and electrophysiological methods, in particular evoked potentials to spinothalamic (laser) input. The region comprising the posterior insula and medial operculum may deserve being considered as a third somatosensory cortex (S3) contributing to the spinothalamic attributes of somatic perception.

Bilateral thalamic stroke transiently reduces arousals and NREM sleep instability.

The vascularization of the human thalami is supplied by many perforating arteries, which exhibit complex distribution and many possible individual variations. One rare variant is the artery of Percheron that supplies the paramedian thalami bilaterally. Its ictal occlusion may result in a symmetric paramedian infarction, which generally leads to impairment of consciousness associated with hypersomnia. Our aim is to describe in detail sleep-wake schedules, sleep structure and microstructure in a 68-year-old patient with occlusion of Percheron's artery. EEG monitoring, performed 24 h after the onset of symptoms, showed severe disruption of the sleep-wake cycle, with episodes of sleep and wakefulness recurring irregularly during day and night. Thalamic nuclei are part of the human arousal system; medial thalamic nuclei play a pivotal role in sleep regulation at different levels. A diagnosis of paramedian thalamic infarction should be considered in patients who present with recurrent episodes of unresponsiveness.

Stuttering after right cerebellar infarction: a case study.

UNLABELLED: We report a male patient with neurogenic stuttering after cerebellar infarction. He had suffered from frontal and thalamus damage and he had exhibited aphasia, but his speech had been fluent until onset of the cerebellar infarction. Results of analysis of speech samples included the following: (1) the patient showed very frequent syllable repetition and part-word repetition. (2) The stuttering occurrence rate at the second test was much higher than at the first test. (3) Almost all stuttering occurred on initial word sounds; stuttering on the medial and final word was less frequent. (4) Adaptation effect was absent. (5) Secondary behaviors such as closing of the eyes and grimacing were observed. The internal model related to cerebellar functions can be modified using feedback-error information. Results suggest that internal model dysfunction caused this patient's stuttering. EDUCATIONAL OBJECTIVES: After reading this text, the reader will be able to: (1) provide characteristics of neurogenic stuttering after the cerebellum infarction; (2) discuss the relationship between neurogenic stuttering and functions of the cerebellum.

Bilateral thalamic lesions.

OBJECTIVE: Bilateral thalamic lesions are rare and relatively obscure neoplasms. We present our experience with nine cases of bilateral thalamic lesions and attempt to analyse them in the background of available literature. MATERIALS AND METHODS: Retrospective analyses of the case records of 9 cases of bilateral thalamic lesions treated in our department since January 2002, which have a minimum of 1 year follow-up. RESULTS: The study group included four males and five females with a mean age of 14.6 years (5 years to 29 years). Seven of these patients had radiological evidence of bilateral thalamic lesions at presentation and 2 patients had involvement of the opposite thalamus at a later stage of the disease. All patients except one presented with raised intracranial pressure symptoms. Focal motor deficits (4/9), behavioral and memory disturbances (3/9) were the other major presenting symptoms. Biopsy confirmation was possible in six patients and histopathology was suggestive of low grade fibrillary astrocytoma in all six patients. Seven patients required CSF diversion procedure for associated hydrocephalus. Eight of our nine patients underwent radiotherapy. On last follow-up, 3 patients were clinically stable with images suggestive of arrested disease, four patients had evidence of progressive disease both clinically and radiologically and there were two recorded cases of mortality. CONCLUSION: Primary bilateral thalamic lesions have characteristic neuroradiological properties and are distinct from unilateral thalamic tumours with bilateral progression. Almost all of these lesions on histology prove to be gliomas but decompressive surgery is seldom feasible. Surgical intervention is limited to biopsy and CSF diversion for hydrocephalus. Bilateral thalamic lesions remain unresponsive to adjuvant therapy and generally carry a poor prognosis.

Intracranial neurostimulation for pain control: a review.

Intracranial neurostimulation for pain relief is most frequently delivered by stimulating the motor cortex, the sensory thalamus, or the periaqueductal and periventricular gray matter. The stimulation of these sites through MCS (motor cortex stimulation) and DBS (deep brain stimulation) has proven effective for treating a number of neuropathic and nociceptive pain states that are not responsive or amenable to other therapies or types of neurostimulation. Prospective randomized clinical trials to confirm the efficacy of these intracranial therapies have not been published. Intracranial neurostimulation is somewhat different than other forms of neurostimulation in that its current primary application is for the treatment of medically intractable movement disorders. However, the increasing use of intracranial neurostimulation for the treatment of chronic pain, especially for pain not responsive to other neuromodulation techniques, reflects the efficacy and relative safety of these intracranial procedures. First employed in 1954, intracranial neurostimulation represents one of the earliest uses of neurostimulation to treat chronic pain that is refractory to medical therapy. Currently, 2 kinds of intracranial neurostimulation are commonly used to control pain: motor cortex stimulation and deep brain stimulation. MCS has shown particular promise in the treatment of trigeminal neuropathic pain and central pain syndromes such as thalamic pain syndrome. DBS may be employed for a number of nociceptive and neuropathic pain states, including cluster headaches, chronic low back pain, failed back surgery syndrome, peripheral neuropathic pain, facial deafferentation pain, and pain that is secondary to brachial plexus avulsion. The unique lack of stimulation-induced perceptual experience with MCS makes MCS uniquely suited for blinded studies of its effectiveness. This article will review the scientific rationale, indications, surgical techniques, and outcomes of intracranial neuromodulation procedures for the treatment of chronic pain.

Clinical features of sporadic fatal insomnia.

Recent advances in neuropathology, genotyping, and physiochemical characterization of proteins have allowed for the classification and verification of MM2-thalamic Creutzfeldt-Jakob disease (CJD). CJD is a fatal neurodegenerative illness belonging to the transmissible spongiform encephalopathies, also known as prion diseases. Sporadic CJD is generally classified by the genotype at codon 129 of the prion protein gene and the distinct physiochemical features of the pathologic prion protein (PrP(sc)). The entity is characterized by methionine homozygosity at codon 129, type 2 PrP(sc), and, primarily, thalamic pathology (MM2-thalamic CJD). It shares clinical and pathologic similarities with the genetic prion disorder fatal familial insomnia; the MM2-thalamic phenotype has therefore been called sporadic fatal insomnia (SFI). SFI may also present like other neurodegenerative diseases, and common diagnostic findings that are seen in other forms of sporadic CJD may be absent.