The Anatomic Localization of Lesions in the Thalamus

Functional Anatomy of the Thalamus

The paired thalamic nuclei are egg-shaped structures of gray matter located on both sides of the third ventricle [92]. They represent the largest portion of the diencephalon; other diencephalic structures are the epithalamus (pineal and habenular complex), the subthalamic nucleus, and the hypothalamus. The thalamus plays a major role in cortical activation [105]. It projects to the cortex in a highly organized fashion. Characteristically, thalamic connections are reciprocal, that is, the target of the axonal projection of any given thalamic nucleus sends back fibers to that nucleus. Nevertheless, thalamocortical projections are often larger than their corticothalamic counterparts (e.g., the geniculocalcarine projection). Anatomically and functionally, four regions can be distinguished in the thalamus: anterior, posterior, medial, and lateral, partially separated from each other by white matter laminae that are visible to the naked eye [74,132]. In the core of the thalamus, a fifth region is encased by these laminae, the intralaminar nuclei [194]. Finally, the lateral aspect of the thalamus is covered by a layer of myelinated axons, the external medullary lamina, housing in its core clusters of cells, the reticular nucleus of the thalamus [182]. A simplified account of the thalamic nuclei and their connections, pertinent to clinical localization, is given in Table 18.1. Figure 18.1 illustrates the position and main cortical projections of the thalamic nuclei.

From a diagnostic standpoint, the complex thalamic anatomy can be divided into four main regions:

1. The midline, intralaminar, reticular, and some areas of the ventral anterior nuclei mediate general cortical alerting responses and are termed nonspecific thalamic nuclei. However, the location and role of thalamic cells providing nonspecific cortical activation is still being worked out [37,79]. By contrast, specific thalamic nuclei receive sensory information from the body, process it, and project the pertinent output to specific areas of the cortex, such as the somatosensory area and visual cortex. The nonspecific thalamic nuclei receive strong projections from the midbrain reticular formation, hypothalamus and the spinothalamic tract as well as from other sensory pathways. Some stimuli (e.g., auditory, pain) excite this alerting system more easily than others (e.g., visual). These nuclei project back to the midbrain and to the specific thalamic nuclei. Lesions that involve these structures bilaterally cause impairment of alertness.

2. The medial (dorsomedial) and anterior thalamic nuclear groups play an important role in memory and emotions [97]. They are connected with the hypothalamus, the “limbic lobe” (cingulate gyrus, medial temporal region, insula), and the frontal lobe. The dorsomedial nucleus mediates olfaction, emotions, the secondary affect of pain, the sleep-wake cycle, and executive functions [7,156,163,170,187,190]. Lesions of the anterior nucleus are more consistently associated with memory and executive function loss [55,63,69].

3. The ventral lateral and basal nuclear groups are concerned with the processing of sensory information and relaying it to the cortex, and with sensorimotor control [108].

A. Relaying sensory information to the cortex is effected mainly by three nuclear groups, as follows:

i. The ventral posterior nuclear group, where taste and somatosensory information is elaborated and projected to the somatosensory cortex of the parietal lobe. Within the thalamus, lateral inhibition increases sharpness in spatial localization. Information from receptors in the head reaches the ventral posterior medial nucleus through the trigeminothalamic pathways. The ventral posterolateral nucleus processes somatosensory information conveyed by the spinothalamic tract and medial lemniscus. A group of nuclei, dorsal to the medial geniculate body and called the ventral medial or caudal nucleus, participate in the perception of pain and temperature, particularly well-localized, sudden pain [12]. Discrete spinothalamic projections also reach other nuclei, including the ventrolateral nucleus [35].

ii. The medial geniculate body, where auditory information from the inferior colliculus passes on to the transverse temporal gyrus, buried in the depth of the Sylvian fissure. Lesions of this thalamic nucleus are discussed in Chapter 11.

iii. The lateral geniculate body, relay station for the visual pathway, which receives from the retinal ganglion cells the axons that form the optic tract and which originates the axons that project to the calcarine cortex through the optic radiations. Lesions of this thalamic nucleus are discussed in Chapter 7.

B. Sensorimotor control is carried out by the more anterior of the ventrolateral nuclei (ventral lateral and ventral anterior) and perhaps by the intralaminar nuclei [93,124].

iv. The ventrolateral nucleus has an oral, a medial and a smaller caudal portion. The medial portion receives input from the cerebellum and projects to the precentral cortex or primary motor cortex (area 4). The largest oral portion receives input from the globus pallidus and projects mostly to the premotor cortex. The ventrolateral nucleus also receives information from musculoskeletal system mechanoreceptors; it contributes to the coordination of finer, distal motor movements with the proximal axial movements that support them.

v. The ventral anterior nucleus may play a role in voluntary attention. It has strong connections with the pallidum, medial thalamic nuclei, and frontal cortex.

            Anatomically, the thalamus constitutes the keystone for two large sensorimotor control loops: (a) the cerebello-rubro-thalamo-cortico-pontocerebellar loop and (b) the cortico-striato-pallido-thalamo-cortical loop. Although the physiologic role of each loop is far from clear, it is known that lesions in each loop cause different syndromes. Obviously, the anatomy allows ample possibilities for lesions to affect both loops. Symptoms and signs derived from cerebellar lesions are discussed in Chapter 16. Those derived from basal ganglia lesions are discussed in Chapter 19. Motor findings that point to the thalamus as the site of the lesion are given preferential attention here.

4. The fourth main region of the thalamus comprises the dorsolateral and posterior nuclear groups, particularly the pulvinar, which seem to modulate occipito-temporo-parietal cortical attention, using an object-based frame of reference [204]. As such, it facilitates visual attention and the cortical attention needed for language- related sensory tasks in the left hemisphere and visuospatial tasks in the right [36,78]. This area is much better developed in humans than in lower mammals. During ontogenesis, it is the last thalamic region to reach adult morphology.

Vascular Supply of the Thalamus

Cerebrovascular disease is the most common cause of discrete thalamic pathology resulting in signs and symptoms of localizing value [165]. Infarcts are more common than hemorrhages. Therefore, some knowledge of the vascular supply of the thalamic nuclei helps greatly to understand the so-called thalamic syndromes and the localization of thalamic lesions.

The thalamic arteries arise from the posterior communicating arteries and from the perimesencephalic segment of the posterior cerebral arteries [25,147–149]. The origin and territory of supply of the various thalamic vessels differ in each person. For instance, when the posterior communicating artery is small or absent, arterial twigs from the posterior cerebral artery supply the thalamic territory that is otherwise supplied by branches of the posterior communicating artery. Table 18.2 summarizes the more common vascular patterns (Fig. 18.2). For this account, the segment of the posterior cerebral artery proximal to the ostium of the posterior communicating artery has been termed the basilar communicating artery [25].

Localization of Ischemic Thalamic Lesions

In localizing ischemic lesions of the thalamus, several points should be kept in mind:

1. The arterial supply for most of the thalamus arises from the vertebrobasilar system, in some cases with a small contribution from the posterior communicating artery [25]. Only the lateral portion and the hilum of the lateral geniculate body are usually fed by the anterior choroidal artery, a branch of the internal carotid artery.

2. Except for the lateral geniculate body, the middle cerebral and anterior choroidal arteries do not supply the thalamus to such an extent that thalamic infarction would result from occlusion of these vessels [148]. Some internal capsular dysfunction, however, may result from occlusion of thalamic vessels [130]. In rare cases the anterior cerebral artery may contribute to the supply of the posterolateral thalamus through a posterior pericallosal vessel, which is anastomotic with the posterolateral choroidal artery.

3. The paramedian thalamic vessels often arise from a single pedicle that originates in one of the basilar communicating arteries (see Fig. 17.2). Thus, unilateral posterior cerebral artery occlusions may result in bilateral paramedian thalamic infarcts [25].

4. The individual pattern in vessel distribution and size will ultimately dictate the presence of one of the syndromes described below.

The arterial territory responsible for a thalamic ischemic infarct may be inferred from the clinical findings, as follows.

Paramedian Territory

Infarcts here tend to involve also the paramedian region of the midbrain. Most often, the syndrome is composed of the clinical triad of somnolent apathy, memory loss, and abnormalities of vertical gaze [73]. Bilateral medial thalamic infarcts account for the behavioral syndrome, and lesions in the area of the rostral interstitial nucleus of the medial longitudinal fasciculus account for the vertical gaze palsy [207]. The following findings may result, depending on the extent and location of the lesion [11,15,25,61,62,65,87,183,207]:

1. Transient loss of consciousness or somnolence; occasionally akinetic mutism

2. Behavioral changes (confusion, agitation, aggression, lack of initiative, disorientation, apathy, manic delirium, a frontal lobe-like syndrome [13])

3. Recent memory loss (with anterograde and retrograde components). Persistent memory loss is observed only with damage of the dominant anterior nucleus or mamillothalamic tract [183]

4. Vertical gaze and convergence disorders (and occasionally blepharospasm)

5. Contralateral hemiataxia, asterixis, or motor weakness

6. Delayed action tremor (occasionally myoclonus or athetosis) in the contralateral limbs

This syndrome is often due to embolic occlusion of the top of the basilar artery or local atheroma at the origin of the posterior cerebral artery [15,20,121,183].

Thalamogeniculate (Lateral Thalamic or Inferolateral Thalamic) Territory

Ischemia in this territory (ventral posterior nucleus, ventral lateral nucleus, and subthalamic region) causes some of the components of the classic thalamic syndrome described by Dejerine and Roussy [15,21,61,62,115,116,122,177,209]:

 1. Hemianesthesia (occasionally, proprioception is spared)

 2. Transient slight hemiparesis

 3. Hemiataxia

 4. Hemiataxia–hypesthesia syndrome

 5. Lack of nonvolitional utilization of the contralateral body (damaged “automatic pilot”)

 6. Dysequilibrium (“thalamic astasia”)

 7. Choreoathetoid movements

 8. Athetoid posture (“thalamic hand”)

 9. Paroxysmal pain (thalamic pain)

10. Homonymous hemianopia (often due to simultaneous medial occipital infarction)

All these findings occur on the side of the body contralateral to the lesioned thalamus. The more severe forms of the syndrome (complete geniculothalamic infarct) accompany proximal occlusion of the posterior cerebral artery [61]. Partial forms (partial geniculothalamic infarct) result from lacunar infarction restricted to one of the penetrating thalamogeniculate vessels [21,61,129] and result in pure sensory or sensorimotor stroke. Disease of such small perforating arteries often accompanies diabetes and chronic hypertension.

Isolated hemiataxia and ipsilateral sensory loss (the hemiataxia–hypesthesia syndrome or thalamic ataxia syndrome) may occur with infarction in the thalamogeniculate territory that involves the lateral part of the thalamus (ventral posterior nucleus and ventral lateral nucleus) [122,177]. The sensory disturbance may be purely subjective, may affect light touch, pain, and temperature sense, or affect light touch, pain, temperature, position, and vibration sense. The contralateral “cerebellar” dysfunction and sensory loss is due to a lesion of the dentatorubrothalamic and ascending sensory pathways into the thalamus [177]. Also, recurrent pure sensory transient ischemic attacks (transient hemihypesthesia) may occur with ventroposterolateral nucleus ischemia [47].

Tuberothalamic (Anterolateral Thalamic) Territory

Infarcts in this territory are due to thalamopolar artery lesions and result primarily in neuropsychological dysfunction [55,61–63]. The following findings may result:

1. Apathy and verbal perseveration, as part of executive function impairment

2. Anterograde memory loss

3. Facial paresis for emotional movement

4. Occasionally, hemiparesis and visual field defects (sensation spared)

5. The superimposition of temporally unrelated information

6. Dysphasia with left-sided lesions

7. Hemineglect and impaired visuospatial processing with right-sided lesions

Bilateral polar artery thalamic infarcts result in apathy, abulia, “frontal lobe” deficits, lethargy, and impaired memory [82].

Territory of the Posterior Choroidal Arteries

These vessels supply the lateral geniculate body, pulvinar, posterior thalamus, and a small posterior portion of the hippocampus and parahippocampal gyri [137]. In lateral posterior choroidal artery territory infarction, the most common clinical manifestations include:

1. Homonymous quadrantanopsia, superior or inferior, or, rarely but particularly suggestive of involvement of the lateral geniculate body in this territory, a homonymous horizontal sectoranopia, tubular or shaped like a wedge

2. Decreased optokinetic nystagmus when moving the drum to the side of the lesion

3. Hemisensory loss with mild hemiparesis

4. Mild hemiparesis, accompanied by sensory loss (although no involvement of the internal capsule is detected by MRI)

5. Transcortical aphasia

Isolated medial posterior choroidal artery territory infarction has not been reliably documented. Miosis, occasionally ipsilateral, has been described with these lesions [137].

Thalamic hemorrhage is discussed in Chapter 21.

Clinical Manifestations of Lesions in the Thalamus

The following considerations facilitate the understanding of the clinical manifestations of thalamic lesions:

1. Because of the smallness of the thalamus, several of the nuclei and even several of the functional regions outlined above are usually affected simultaneously, even by discrete lesions such as infarcts. Because arteriolar vascular territories cross the nuclear boundaries, as a rule ischemic disease affects several nuclei, often partially [25]. In addition, many lesions are not restricted to the thalamus, but involve neighboring areas of the brain as well. Paramedian thalamic vascular lesions tend to affect also the midbrain, with a resultant decrease in the level of alertness to the point of coma [25]. Thus, other motor or sensory findings that would point to thalamic involvement cannot be elicited. Laterally located lesions may disrupt the internal capsule, thereby causing motor and sensory deficits [64] that mask the deficits characteristically present with thalamic involvement. For instance, the tendency to avoid using an otherwise strong limb contralateral to a lesioned ventral lateral thalamic area (“thalamic neglect”) is not manifest if capsular involvement has resulted in a hemiparesis. Lesions extending inferiorly may yield hemiballismus, for which the subthalamic lesion is probably primarily responsible. Lesions in the territory of the lateral posterior choroidal artery may cause memory loss through involvement of the parahippocampal gyrus [137].

2. Except for sensory deficits, unilateral thalamic lesions result in transient deficits. By contrast, bilateral lesions or unilateral lesions, such as hemorrhages or tumors, which press against the contralateral thalamus or impinge on the midbrain, may render the patient comatose or akinetic and mute.

3. Timing has a particular impact on the clinical expression of thalamic lesions. As the effects of an acute lesion recede, neglect may disappear, inability to walk may yield to mild ataxia, and hemisensory loss diminishes. Other findings, however, particularly the so-called positive symptoms (tremor, pain), usually become more pronounced within a few weeks after the injury.

Discrete lesions in various regions of the thalamus, and, more recently, deep brain stimulation through implanted electrodes, are increasingly used for the treatment of parkinsonian and essential tremor [144,199], dystonia [91], pain [34], epilepsy [188], and the manifestations of Gilles de la Tourette syndrome [154,186]. Tremor treatment is the most extensively used and best understood deep brain stimulation thalamic procedure. Essential tremor can be treated by deep brain stimulation with electrodes in the ventrolateral nucleus. The ventrolateral nucleus includes the nuclei ventralis intermedius and ventralis oralis posterior. The ideal location of the stimulating electrodes seems to lie in the ventralis oralis posterior nucleus immediately anterior to the cerebellar receiving area, ventralis intermedius [144]. In addition to the target effect, some of these procedures have produced other symptoms or signs, which will be mentioned under the appropriate heading.

Disturbances of Alertness

Sudden bilateral paramedian thalamic lesions, such as infarcts, may cause a decreased level of alertness ranging from somnolence to coma [25,61,106], generally transient. Prolonged coma may result if the lesion extends into the midbrain tegmentum. These patients often have oculomotor paresis [25]. By contrast, patients with pure thalamic involvement have very small reactive pupils (“diencephalic pupil”), and their extraocular movements, elicited by the doll’s head maneuver, are full [152]. Akinetic mutism, discussed in Chapter 23, may follow bilateral paramedian thalamic lesions [25,171], as in the noted Karen Quinlan case [90].

The intralaminar, reticular, and ventral anterior nuclei seem to play the greatest role in mediating normal alertness [67,182]. Electrical stimulation of this region induces arousal from sleep [208], while lesions here cause drowsiness [71]. Bilateral paramedian thalamic infarction may cause severe apathy and a bromocriptine-responsive compulsive tendency to assume a sleeping posture (“presleep behavior”) [26]. In patients with paramedian thalamic lesions and daytime hypersomia, REM sleep is normal, but wakefulness, sleep spindling and stages of deep sleep are all reduced, suggesting that the medial thalamus is the “final common pathway” for both maintenance of wakefulness and promotion of non-REM sleep [7,174]. Other reported disturbances include inversion of the nycthemeral rhythm and dissociation of sleep stages, detected by electroencephalography, between the two hemispheres: the hemisphere affected by a thalamic tumor showed earlier onset of deeper sleep stages [81]. Normally, thalamic deactivation at sleep onset precedes that of the cerebral cortex [109]. The intralaminar nuclei of the thalamus are involved in the genesis of unconsciousness with seizures [192]. Low-frequency (3/s), high-intensity combined stimulation of the right centromedian nucleus and left nonspecific mesencephalic ascending pathways elicits a response similar to the typical absence attack [197]. The dorsomedial thalamic nucleus may have reduced volume and be hypometabolic on the side of chronic temporal lobe epilepsy [80].

Fatal familial insomnia, a prion disease related to mutations in the PRNP gene on chromosome 20, is mostly confined to the anterior and dorsomedial thalamic nuclei but also involves the intralaminar nuclei [131]. It is characterized by progressive insomnia, loss of slow-wave sleep and abnormal REM sleep behavior, a loss of vegetative and endocrine circadian rhythms, and dysautonomia (hyperhidrosis, hyperthermia, tachycardia, hypertension, miosis, and sphincter disturbances). These disturbances are associated with impaired arousal during daytime, dreamlike states, motor abnormalities (dysarthria, ataxia, pyramidal dysfunction, intention tremor, myoclonus), and eventual coma and death [131].

Autonomic Disturbances

Deep brain stimulation with electrodes in the centromedian-DM thalamic region caused a change in penile erection, facilitating it in a patient and inhibiting it in another [186]. In both these cases deep brain stimulation improved the tics of Gilles de la Tourette syndrome, where an abnormality of anterior thalamic dopamine activity has been detected [180]. Kleine-Levin syndrome, which is characterized by episodes of somnolence, hyperphagia, impaired recent memory, and hypersexual behavior, traditionally believed to be related to hypothalamic disease, may be due to paramedian thalamic lesions [24].

Disturbances of Mood and Affect

Apathy, disinterest, and a lack of drive have been reported with lesions of the paramedian region of the thalamus [13,25,61,87], which is involved in reward learning [160]. Less often, such lesions may cause agitation, dysphoria, or an acute confusional state [13,57], and even undue joviality, accompanied by confabulation [25]. Similar manifestations of bilateral medial thalamic damage may be interpreted as a partial Klüver-Bucy syndrome, described in a patient with chronic amnesia, distractibility, hyperorality, affective dyscontrol, and a socially inappropriate behavior [134]. A manic-like state with disinhibition affecting speech (with logorrhea, delirium, joking, laughing, inappropriate comments, and confabulation) has been described with right thalamic lesions [13,94]. A patient mentioned having lost the pleasure involved in reading after a left anterior thalamic infarct [32]. The ipsilateral cingulate gyrus was hypometabolic. In schizophrenia, a disorder with altered affect and executive function, neuronal loss has been found in the dorsomedial and anterior nuclei of the thalamus by some [153,210], but not by others [44].

Memory Disturbances

Recent memory may be transiently or permanently impaired by lesions of the anterior or medial thalamic nuclear region [25,62,63,76,127,198]. This deficit appears most consistently with bilateral lesions but may be associated with even unilateral lesions of either thalamus [25,32,145]. In some cases, the transient nature of the deficit has prompted the diagnosis of transient global amnesia, although most patients with this disorder do not present evidence of thalamic disease [59,157].

The proposed anatomic basis for a permanent amnestic syndrome after bilateral anterior thalamic infarctions is combined damage to hippocampal– thalamic pathways via the mammillothalamic tract and medial temporal–thalamic pathways via the inferior thalamic pedicle [63,68,110,195,200]. These pathways are closely adjacent in the anterior thalamus, and bilateral lesions that cause amnesia are found in this region, whereas bilateral medial thalamic lesions that do not cause amnesia are located more posteriorly [63,110,125,200]. Korsakoff’s amnesia correlates with neuronal loss in the anterior thalamic, but not dorsomedial, nuclei [69]. Pure amnesia has also been described after a unilateral left polar thalamic infarct affecting the anterior thalamic nuclei and adjacent mammillothalamic tract [32]. Lesions involving the left thalamus affect mainly verbal memory [55,133], whereas those in the nondominant paramedian thalamic region impair memory related to visuospatial tasks (nonverbal memory) [13,150,178,179,206].

Thalamic amnesia is characterized by deficits in anterograde verbal and visual learning and in retrograde amnesia, but motor learning is preserved [63]. Patients who are alert and active usually perform adequately in tests of immediate memory, such as digit span. Characteristically, the amnesia is most profound for events taking place after the injury (anterograde amnesia or recent memory loss), although sometimes it includes information acquired from days to years previously (retrograde amnesia) [55,83,120,211]. Disorientation to time is common. With thalamic lesions, the content of recall is not as affected as the temporal order of the items stored in memory, be they verbal or nonverbal items. Thus, the patients may retrieve facts, but in a disorganized fashion and out of context [55,175]. Some patients seem to be aware of their deficit [211], and others do not [198]. Whether this can be accounted for by differences in the site or extent of the lesion remains to be determined.

Some unusual patterns of memory loss and recovery have been described with thalamic lesions. A patient with bilateral medial thalamic lesions recognized by their voices relatives whom he had failed to identify visually (prosopagnosia) [120]. Another patient’s retrograde amnesia improved suddenly one year after a left anterior thalamic infarction, when he was exposed to an event that triggered the recall of a flood of previously forgotten autobiographical detail [107]. The resemblance with Proust’s recollection triggered by the taste of aunt Leonie’s “petite madeleines” has led to the term “petite madeleines phenomenon” for this remarkable presentation [107].

Confabulation, or falsification of memory occurring in clear consciousness, is frequently present with thalamic amnesia [13,55,167,168]. Patients may confabulate spontaneously or when asked to recall some facts [167,168]. Particularly those that confabulate spontaneously seem to have an impaired ability to order in time facts retained in memory [55,168]. Part of the problem has to do with identifying the relevance of items stored in memory to the current context. Items of memory that are not appropriate for the here and now find their way into the patient’s verbal output or are manifested by behavior that relates to past experiences, but not to what is now appropriate.

Sensory Disturbances

Thalamic lesions may cause sensory loss, often accompanied by paresthesias and pain.

PARESTHESIAS AND PAIN

Clinically, small lesions in the ventral posterior lateral nucleus of the thalamus may yield only contralateral paresthesias that lack “objective” sensory loss when tested at the bedside [49]. Such paresthesias tend to occur on one side of the face, particularly around the mouth, and in the distal portion of the limbs. Occasionally, this cheiro-oral or distal distribution of the paresthesias may suggest a more distal lesion (e.g., radiculopathy) [98]. These areas of the body have the largest representation in the thalamic sensory nuclei. When the trunk is also numb, the subjective feeling of numbness may stop abruptly in the midline, although on objective testing the sensory loss often fades toward the midline [130]. Such a “thalamic midline split,” which is absent with parietal lesions, has been thought to have some clinical value in identifying the site of the lesion [129]. The numb areas of the body may feel swollen, enlarged, shortened, twisted, or torn, or they may tingle. Objects held with the limb contralateral to the lesion may feel abnormally heavy. Finally, the patient may be unaware of a profound sensory loss.

Pain referred to as thalamic pain is perhaps the best known component of Dejerine and Roussy’s thalamic syndrome, described above [119,209]. The unpleasant or excruciatingly painful sensation on the side of the body contralateral to a thalamic lesion (an infarct is most common) may appear at the time of the injury [49] or when the sensory loss begins to improve. The pain feels localized to the skin. Cutaneous stimuli trigger paroxysmal exacerbations of the pain, which persists after the stimulus has been removed. The latency between the stimulus and pain perception is prolonged, suggesting that the pathways conveying it are polysynaptic. Because the perception of epicritic pain, such as that induced with a pin-prick, is reduced on the painful areas, this symptom has been termed anesthesia dolorosa, or painful anesthesia. A similar symptom may follow damage of the posterior root ganglia (herpes zoster) or trigeminal nerve or nucleus (trigeminal neuralgia with anesthesia). Ventral-posterior thalamic nuclear lesions are more likely to produce half-body pain than lesions elsewhere in the sensory pathways [17]. The lesion may be restricted to the ventral-posterior nucleus (ventral caudal nucleus in Schaltenbrand’s terminology [164]) and it is generally accompanied by hypesthesia to cold but not to heat [88]. Metabolic studies have shown enhanced activation of somatosensory cortex with stimulation [88] or pain relief correlating with increased metabolic rates in prefrontal and anterior insular cortices, hypothalamus and periaqueductal gray [95], all of them structures felt to play an important role in pain perception. Some patients with localized neuropathic pain can be relieved by stimulation of the basal ventroposteromedial region of the thalamus or by lesioning the sensorimotor cortex [88].

Thalamic pain seldom occurs with tumors. It has been described most often with vascular lesions, some of which involve not only the thalamus but also the deep parietal white matter [2]. Besides, delayed pain may follow cortical parietal infarcts, particularly those in the bank of the Sylvian fissure, affecting the second somatosensory area (pseudothalamic syndrome) [10,166].

LOSS OF SENSORY MODALITIES

All somatosensory modalities are processed in the ventral posterior nucleus of the thalamus contralateral to the side of the body where they are perceived. Within the nucleus there is a definite topographic distribution: the head is represented anteroinferomedially, whereas the leg is represented posterosuperolaterally; the arm is represented in an intermediate position. A larger volume of the nucleus is dedicated to the mouth, tongue, and distal portion of the extremities; their thalamic representation is almost completely crossed. The large oral thalamic and cortical representation in humans may well be related to language functions [27]. The face, proximal portion of the limbs, and trunk are represented in a smaller volume of thalamic tissue, mainly contralateral but partially ipsilateral [18]. Thalamic sensory loss tends to occur maximally in the distal portion of the limbs and often spares the face [89]. Such sparing may be related to the different vascular supply of this portion of the ventroposterior region (paramedian territory) or to the bilateral thalamic representation of the face.

In regard to the thalamic topography of various sensory modalities, physiologic experimental studies have shown that cells concerned with deep pressure and movements of the limbs are preferentially located in the rostral and caudal ends of the ventral posterior lateral nucleus. The central part of the nucleus contains neurons that respond to cutaneous stimuli. In humans, however, lesions large enough to produce any sensory loss most often involve several modalities. No existent clinicopathologic studies allow precise identification of thalamic areas for touch versus joint position or vibration. Pain sensation has been obtained by stimulation of the basal part of the nucleus [18].

Because the perception of pin-prick, temperature, touch, or vibration is altered more often after thalamic than after cortical lesions, these sensory modalities have been termed primary or thalamic. By contrast, conscious joint position identification, two-point discrimination, stereognosis, and graphesthesia tend to be more impaired after cortical parietal lesions, and are thus termed secondary or cortical sensory modalities. Nevertheless, parietal lesions often cause some impairment of thalamic modalities and vice versa. Occasionally, a lesion in the thalamus may disturb mainly the so-called cortical sensory modalities [51,203].

Anesthesia and impaired temperature perception tend to occur with basal lesions near the medial geniculate body [17,18]. Because vibration sense remains unaltered after surgical removal of the parietal cortex, it has been assumed that hemispheric lesions causing loss of vibratory sense necessarily implicate the thalamus or the thalamocortical projections [161].

Decreased thalamic perfusion has been observed with hysterical hemisensory loss [201]. This abnormality reverted when the patients improved.

Disturbances of vision and hearing are discussed in Chapters 7 and 11. Visual field defects caused by thalamic lesions frequently involve the superior quadrant bilaterally. An intolerance to light (“central dazzle”) has been ascribed to a thalamic lesion [38,42]. Paramedian thalamic infarction may cause the sudden onset of vivid, formed visual hallucinations (suggesting peduncular hallucinosis) associated with agitation and sleep disturbance (MRI revealed no abnormality of the midbrain or cerebral peduncles) [46]. Vivid visual hallucinations, suggesting peduncular hallucinosis, with left hemiparesis and left paresthesias have been described with a right posterior thalamic infarct [173]. Auditory and visual experiential hallucinations may occur with unilateral thalamic lesions affecting the intralaminar and dorsomedial nuclei [112,139]. Auditory illusions of hyperacusis and palinacousis may occur with a lesion in the medial geniculate body [52]. Auditory-tactile synesthesia followed a lesion centered in the ventrolateral nucleus [9]. Unilateral visual sensory neglect may occur with lesions of the right pulvinar [85,193].

Normal detection, but altered identification, of smells has been associated with thalamic lesions; in several patients, odors and taste were perceived either in a neutral way, their pleasant character having disappeared, or as unpleasant [162,172]. Taste sensations have been elicited in humans by stimulation of a portion of the ventro-postero-medial nucleus [101].

Motor Disturbances

Just as the sensory disturbances described in the previous section can be related to lesions in the ventral posterior nucleus of the thalamus, motor disturbances can be related to lesions of the ventral lateral nucleus and the adjacent subthalamic region.

POSTURAL DISTURBANCES

Following an acute thalamic lesion, even a unilateral lesion, patients may be transiently unable to stand or even sit, despite normal strength of the limbs when tested against resistance (thalamic astasia) [115,116,196]. The lesions, including infarction, hemorrhage, or tumor, primarily involved the superoposterolateral thalamus and spared the rubral region. Although alert, with normal or near-normal strength and a variable degree of sensory loss, patients with thalamic astasia cannot stand, and often cannot even sit up unassisted. They fall backward or toward the side contralateral to the lesion and appear to have a deficit of overlearned motor activity of an axial and postural nature [116]. Sudden falling to one side while sitting, standing, or walking has also been described with basal ganglia lesions contralateral to the side of the fall [96]. Some patients with posterolateral thalamic lesions push actively to the side contralateral to the lesion (pusher syndrome) [86]. The postural disturbance of thalamic lesions may be accompanied by a disturbance in the patient’s perception of the vertical axis [39,40,84].

Postural abnormalities in patients with lesions in the ventrolateral nucleus or its connections with the medial frontal region, in the suprathalamic white matter, go beyond simple disequilibrium [115,116]. Volitional movements, like trying to overcome the strength of the examiner during isometric testing, are normal. Yet the patient does not use the same strong limbs, and particularly the axial muscles, in tasks that are normally performed automatically or without much thinking, such as shifting in bed. Proximal movements that normally support distal ones, such as abduction of the shoulder when trying to pick up a cup, are restricted, even though the patient is perfectly able to abduct his or her shoulder on command. This syndrome occurs with lesions of either thalamus and is different from the sensory hemineglect described predominantly with nondominant thalamic lesions [85,116]. It has been called motor neglect [111]. Neglect to use the limbs contralateral to the lesion may convey to the examiner the false impression that the patient is hemiplegic [6,13,15,146,205,206]. Certainly large infarcts, lacunes [129], hematomas [203], and tumors may involve the neighboring internal capsule, causing a more or less profound hemiplegia. However, purely thalamic involvement does not result in hemiparesis. Lesions in the ventral lateral nucleus of the thalamus cause contralateral hypotonia, reduction of emotional expression, and transient neglect [71,111]. This syndrome may occur even with lesions that are discrete enough to spare all sensory modalities and the early (thalamic) components of the somatosensory evoked response. Such lesions, which are circumscribed to the ventral lateral nucleus, spare the ventral posterior nucleus. Because the late components of the somatosensory evoked response are abolished, it has been postulated that the ventral lateral nucleus plays a key role in the activation of the frontal cortex. Unilateral thalamic lesions cause akinesia, either as a result of sensory inattention or as a consequence of impaired activation of axial, automatic synergies, as described above [15,115,196,206].

Lesions of the thalamus may cause emotional facial paresis (i.e., weakness of emotionally evoked facial movements, such as smiling, with normal volitional activation) [75]. Contralateral emotional facial paresis has been described with lesions of the thalamus and subthalamus, anterolateral thalamus and insula, posterior thalamus and operculum, and posterior thalamus [14,15,62,75].

Damage to the dentatorubrothalamic projection to the ventral lateral nucleus by a lesion rostral to the decussation of the superior cerebellar peduncle or damage to the ventral lateral nucleus itself results in hemiataxia (coarse, with action tremor, dysmetria, dysdiadochokinesia, and rebound) of the contralateral limbs [113]. These structures are near the corticospinal pathways and the ventral posterior nucleus of the thalamus, explaining why the hemiataxia is associated with hemiparesis or hypesthesia in this type of infarct [123]. Isolated hemiataxia and ipsilateral sensory loss (the hemiataxia-hypesthesia syndrome) may be a manifestation of thalamic infarction in the thalamogeniculate territory causing damage to the ventral posterior nucleus and ventral lateral nucleus [122]. The cerebellar syndrome is not as severe as with involvement of the superior cerebellar peduncle or dentate nucleus. Regarding hand movements, pinching may be involved in both cases, but reaching tends to be spared with thalamic lesions [8]. Some weeks after the injury (which is most often ischemic), tremor at a rate of between three and five cycles per second may appear in the affected extremities [128]. It is mainly distal and increases greatly during the performance of any movement. This tremor may be abolished by DBI or by a surgical lesion of the ventral lateral nucleus of the thalamus [169]. If the central tegmental tract is also involved, tremor with a similar rate may affect the eyelids, eyes, or palate (“palatal myoclonus or tremor”). Central tegmental tract lesions are in the territory of the thalamopeduncular paramedian vessels and are often related to occlusion of the top of the basilar artery [25]. Contralateral cerebellar ataxia and proprioceptive sensory loss may occur with lesions of the ventroposterior thalamus, likely due to interruption of cerebellar outflow pathways in the thalamus rather than to sensory deafferentation [66].

Lesions that are slightly more rostral, involving the subthalamic region and the pallidothalamic projections to the ventral lateral nucleus, may cause transient contralateral hemiballismus [94]. After some days or weeks, the amplitude of the movement decreases and either disappears or adopts a choreic or athetotic pattern.

Dystonia may be secondary to a necrotizing lesion or to degeneration, as with the familial dystonias. Messenger RNA for torsinA, a protein encoded by the gene abnormal in early-onset torsion dystonia, is abundantly present in the thalamus [4]. Thalamic infarcts in the intermediate and caudal portions of the ventrolateral nucleus may cause myoclonic dystonia in the contralateral limbs [54,93,99,103]. The myoclonic nature of the deficit, often accompanied by action tremor or chorea, differs from the dystonia with tonic spasms more characteristic of striatopallidal lesions [93,99]. The onset of the dystonic movements often lags by months or years after the acute insult [54,56]. Dystonic tremor with chronic MRI evidence of infarction in the anterior nucleus of the thalamus may have resulted from a more posteroventral lesion causing atrophy but no cavitary lesions in the involved nuclei [30]. The sensory fields of thalamic neurons are enlarged in patients with dystonia [100,102]. Patients with secondary dystonia or hemiballismus of basal ganglionic origin tend to improve with lesions or stimulation of the ventrolateral nucleus of the thalamus [23].

Abnormal posturing of the hand, often termed thalamic hand, may appear two or more weeks after the occurrence of a vascular lesion of the same region. The hand assumes a posture with flexion at the wrist and metacarpophalangeal joints, whereas the interphalangeal joints are hyperextended. Flexion of the metacarpophalangeal joints increases from the second digit, which may actually be extended, to the fifth digit, which is markedly flexed. The fingers may be forcibly abducted. The thumb is either abducted or pushed against the palm [114].

Other abnormal movements described with thalamic lesions include action myoclonus [5], ideomotor apraxia [136], and asterixis [19,41,116,181]. Asterixis is more common with ventrolateral nucleus lesions [184]. Hyperekplexia, the sudden loss of postural tone caused by startling stimuli, may be exacerbated with thalamic lesions [45]. Imitation synkineses, also called mirror movements, are common after thalamic lesions [117]. In such cases the distal portion of the limb contralateral to the thalamic lesion tends to imitate the movement performed by the healthy side. When the patient forcibly makes a fist with the sound hand, the fingers of the other hand curl up into the palm, and the patient ends by making a fist with both hands. Loss of position sense or loss of cortical activation by the thalamus may underlie these abnormal movements, which can be decreased, like the choreic movements described above, when the patient concentrates his attention on avoiding them.

A decreased corneal reflex may be present in patients with hemiparesis and hemisensory loss due to a cerebral hemispheric lesion [48]. Loss of parietal excitatory influence on the lower brainstem seems to be responsible for this finding [141]. Pure thalamic lesions, even those that cause a marked hemisensory loss, do not depress the corneal reflex [142]. However, a patient with an acute thalamocapsular lesion had bilaterally depressed late components of the blink reflex when the side contralateral to the lesion was stimulated [29]. It is possible that damage of corticopontine fibers traveling in the internal capsule may be responsible for the deficit.

Small surgical lesions or chronic stimulation of the ventrolateral nucleus of the thalamus may ameliorate drug-resistant tremor [169].

Disturbances of Ocular Motility

Lesions restricted to the thalamus cause only subtle changes in ocular motility [143]. Visual information from the superior colliculus, relayed by the pulvinar to the parietal lobe (“second visual system”), contributes to the detection and localization of visual events in space and to the production of saccadic eye movements that allow the “first” (geniculostriate) visual system to identify such events. Lesions in the pulvinar have been said to cause (a) a decrease in the critical flicker frequency and neglect of visual objects in the periphery of the contralateral visual field, (b) prolonged latency of visually evoked saccadic eye movements, and (c) a paucity of spontaneous eye movements directed toward the contralateral hemifield [212].

Much more striking, and more obvious at the bedside, are eye movement abnormalities that occur when a lesion involves the midbrain and thalamus; this often happens with paramedian thalamopeduncular infarcts [25]. In such cases, impairment of ocular motor function results in abnormal pupils, ptosis, and restriction of vertical eye movements and of adduction. Selective upgaze, downgaze, or combined dysfunction may occur [15], as may blepharospasm [155], bilateral internuclear ophthalmoplegia with ptosis [15], and pseudo-sixth nerve palsy [20] (see Chapter 8). Thalamic lesions may be associated with vertical gaze palsies not because of thalamic injury per se but because of extension of the lesions into the upper midbrain [176]. A “vertical one-and-a-half syndrome” (vertical palsy in one eye, upward palsy in the other eye) may occur [14,15,183]. Bilateral medial thalamic lesions may cause purely vertical saccadic apraxia, affecting volitional vertical saccades but not saccades elicited by external stimuli [127]. Acute thalamic esotropia, with impaired upward gaze, has been described with infarction of the contralateral posterior thalamus in the basilar-communicating artery territory [58]. Tonic activation of the medial rectus in this case could result from damage to direct inhibitory projections from the thalamus or impairment of inputs to midbrain neurons involved with vergence control [58].

Large thalamic hemorrhages may impinge on the midbrain or impair its function by causing raised intracranial pressure [57]. The eyes then become tonically deviated down and slightly adducted, as if peering at the tip of the nose [203]. In some instances, the eyes may be tonically deviated to the side of the hemiparesis, opposite a thalamic hemorrhage (“wrong-way eyes”) [50,189]. This finding has also been reported in extrathalamic supratentorial lesions [151,189].

Deep brain stimulation for the treatment of epilepsy, with electrodes placed at the mesodiencephalic junction, just inferior to the centromedian nucleus of the thalamus, may cause nystagmus with constant velocity slow phases, beating to the right when the left thalamus is stimulated and vice versa [185].

Depression of the reticular activating system (most often metabolic in nature) or involvement of both thalami results in small pupils (1 mm in diameter) that react well to light (diencephalic pupils) [152]. Anisocoria is occasionally present, with the smaller pupil ipsilateral to the thalamic lesion.

Disturbances of Complex Sensorimotor Functions

The thalamus modulates the association cortex involved in the processing of language and other “higher” cortical functions. Although compared with large cortical lesions, unilateral thalamic lesions do not impair these functions as much; the pattern of impairment has some localizing value. Mention has already been made of the contralateral motor neglect caused by lesions in the ventral lateral nucleus of the thalamus and of the contralateral visual inattention that results from lesions in the pulvinar.

Patients with right thalamic lesions may have constructional apraxia and display marked neglect of the left hemifield [205,206]. This hemineglect may be associated with anosognosia and asomatognosia, thus mimicking a parietal lobe lesion [13,205], and is likely due to damage to the intralaminar and ventrolateral or ventral anterior nuclei on the right [31,206]. Right thalamic lesions can also cause impairment in the identification of emotional facial expressions with preserved discrimination of facial identity (prosopoaffective agnosia) [202]. Alexia related to impaired visuospatial perception has been described after right thalamooccipital infarction [72]. Optic ataxia or visuomotor apraxia has been described in a patient with CT evidence of bilateral lesions in the pulvinar, the one on the left in the acute stage when the patient was studied [33].

Dominant-hemisphere thalamic lesions may cause a transient language disturbance (thalamic aphasia) [15,60,77,191] characterized by (a) reduced spontaneous speech with paraphasic errors and perseveration, (b) varying degrees of auditory comprehension impairment, (c) preserved repetition and reading, (d) defective spontaneous writing and writing to dictation but normal copying, (e) word-production anomia but spared word selection and word symbolism, and (f) distractibility. This deficit, which would be classified as a mixed transcortical aphasia, tends to improve in a few weeks [3,22,77]. The language deficit may have more semantic components when the lesion is posterior [158] and more motor components when the lesion affects the anterior nucleus [55]. Electrical stimulation of the ventrolateral thalamus produces an acceleration of speaking. The patient feels urged to speak faster [71]. Stimulation also enhances later recall of objects presented to the patient. The left thalamus is involved in attention mechanisms that gate storage and retrieval of both long-term and short-term verbal memory [78]. Derangement of a specific cortical attention mechanism because of the thalamic lesion results in a lack of drive to speak and perseveration of apparently unrelated verbal material [159]. Some patients have hypophonia and dysarthria [55]. Such language impairment resembles the language impairment that results from left medial frontal lesions [16,118]. Other dorsomedial thalamic lesions cause a bizarre language pattern, with some characteristics of dysfunction in the prefrontal cortex. It contains intrusions (segments of speech out of context) and other evidence of temporal gating impairment, such as giving biographical information while working on a calculation test [28,55]. Apraxic agraphia has been described with an MRI showing a dorsomedial thalamic lesion [140].

The language impairment noted with left thalamic lesions and the visual neglect noted with right thalamic lesions are associated with decreased activity of ipsilateral frontal or temporoparietal association cortex [6,126,140,146]. Deafferentation of an otherwise intact cortex (diaschisis) due to the thalamic lesion may explain these “cortical” syndromes with thalamic lesions. For example, thalamic aphasia may be due to decreased cortical activation secondary to the subcortical lesion [6,126,146]. Some authors ascribe to thalamic lesions or thalamocortical disconnection the cases of striatocapsular aphasia reported in the literature [135].

A stuttering-like repetitive speech disorder may occur with infarction in the paramedian thalami and midbrain [1]. Although the speech disorder seems like stuttering, the compulsive repetitions, constant rate, and monotonous tone seen with these infarctions are not associated with ordinary stuttering. The repetitive speech disorder in patients with infarcts in the supplementary motor area have similar clinical features [1].

Disturbances of Executive Function

Paramedian thalamic infarction may cause a lack of initiative and “frontal lobe” utilization behavior (see Chap. 20), suggesting a thalamofrontal component to environmental interactions that requires inhibition, self-monitoring, and cognitive flexibility [43,55,70]. The patients’ language may appear bizarre because of the presence of intrusions (segments of speech out of context) and the superimposition of mental activities normally processed sequentially, for instance, giving biographical information while working on a calculation test [28,55]. Failure of goal-directed regulation of behavior has been observed with a lesion affecting the right anteroventral thalamic region [138]. A left-sided discrete infarction of the medial thalamus may cause severe impairment of complex executive behaviors, probably due to dysfunction of thalamofrontal linkages that help modulate complex human behavior [163]. Repetitive movements (“clonic perseveration”) may be a manifestation of executive function disorder with thalamic lesions [53].

Infarction of the dorsomedial nucleus, intralaminar nuclei, and medial part of the ventrolateral nuclei is often associated with marked hypoperfusion of the overlying frontal region cortex on PET or SPECT [28,70]. It is thought that the “frontal lobe-like” syndrome with thalamic lesions may be related to impaired activation of the frontal lobe by the damaged dorsomedial and anterior thalamic nuclei [13,195], or their projections, for instance with traumatic brain injury [104]. These nuclei provide an important pathway for information from vegetative centers to reach the frontal lobe.

Topographic Localization of Thalamic Lesions

Following the detailed and referenced account of the localization of thalamic symptoms and signs, a brief synopsis follows organized by the anatomical regions of the thalamus.

Anterior Thalamic Region

Discrete lesions may be silent or cause language disturbances when they affect the dominant hemisphere. They may also cause inattention, which results more often when the right hemisphere is involved. Bilateral lesions may cause akinesia, amnesia, and attentional disturbances. Lesions extending to the subthalamic area may cause athetosis, chorea, or postural abnormalities (thalamic hand).

Medial Thalamic Region

Lesions in this location may pass unnoticed when they are small and unilateral. Large or bilateral lesions cause impairment of recent memory, apathy or agitation, attention derangements, and somnolence or coma. Lesions that extend to the midbrain– diencephalic junction may cause contralateral tremor and vertical gaze palsy, affecting particularly downward gaze.

Ventrolateral Thalamic Region

Sensory loss, paroxysmal pains, and hemiataxia in the contralateral side of the body are the most striking sequelae of lesions in the posterior portion of this region. More anterior lesions cause postural abnormalities, such as disequilibrium and restriction of axial supportive movements or delayed tremor. Hemineglect and language disturbances may appear transiently.

Posterior Region

Basal lesions in this region may cause hemianesthesia, “thalamic pain,” and visual field defects. Dorsal lesions give rise to attentional disorders of the ipsilateral hemisphere, resulting in transient aphasia when the dominant hemisphere is involved. Some patients may have myoclonic dystonia.

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