To study clinicopathologic correlations of thalamic lesions, it is generally agreed upon that patients with thalamic infarcts provide the most precise information. Other lesions, such as bleeds, gliomas, or encephalitis, tend to be more diffuse. Therefore, the study of thalamic strokes provides the best structure–function correlation available and is probably the most useful approach for the clinician, since thalamic infarcts represent the most common pathology encountered.
Although a precise functional correlation for each thalamic nucleus is not possible, as infarcts usually involve multiple nuclei, and since arterial territories have both variability and overlap, it is possible to delineate in broad terms several thal- amic stroke syndromes. This delineation is based on the differ- ent vascular territories of the thalamus. Therefore, in an attempt
to be interactive, we pose the question: what are the vascular territories of the thalamus?
Anatomists such as Foix and Hillemand, and later Percheron (among others) have delineated four main arterial territories in the thalamus based on the arteries that supply it (see Fig. 6.6). A simplified description of them is provided, giving the main areas supplied in each territory (seeFig. 6.7). (1) The territory of the tuberothalamic artery (also known as
the polar artery of Percheron and the premammillary pedi- cle of Foix and Hillemand). The tuberothalamic artery ori- ginates from the posterior communicating artery. It follows the course of the mammillothalamic tracts and supplies predominantly the anterior portion of the thala- mus, including the anterior nucleus, the ventral anterior (VA) nucleus, part of the ventrolateral (VL) nucleus, the ventral part of the dorsomedial (DM) nucleus, the mammil- lothalamic tract, and the ventral amygdalofugal pathway. This vascular territory is known as the anterior territory. (2) The territory of the paramedian artery (also known as
the paramedian pedicle, the retromammillary pedicle of Foix and Hillemand, or the posterior thalamosubthalamic paramedian artery of Percheron). Now you see why we will just refer to it as the paramedian artery. This artery arises from the P1 portion of the posterior cerebral artery, as part of a group of so-called interpeduncular branches or rami. The inferior and middle rami supply the mid- brain, while the superior ramus is the paramedian artery. The paramedian artery runs from the ventromedial aspect of the thalamus to its dorsolateral portion. It supplies most of the dorsomedial nucleus, and portions of the internal medullary lamina, and most of the intralaminar Fig. 6.6. The thalamus is supplied by four main arteries, which divide it into four vascular territories. These are the tuberothalamic artery, the paramedian artery, the inferolateral arterial group, and the lateral posterior choroidal arterial group. (Figure adapted from Schmahmann, J. D. Vascular syndromes of the thalamus. Stroke 2003; 34(9):2264–2291.
nuclei. This vascular territory is known as the paramedian territory.
It is noted that in about one-third of patients, the tuber- othalamic artery is absent, and its territory is also supplied by the paramedian artery.
(3) The territory of the inferolateral arteries (also known as the thalamogeniculate pedicle of Foix and Hillemand, or simply the thalamogeniculate perforators). These are mul- tiple arteries arising from the P2 portion of the posterior cerebral artery (i.e., the portion distal to the posterior communicating artery). The inferolateral arteries mainly supply the ventral posterior nuclear group (VPM and VPL), and also contribute to the supply of the medial geniculate nucleus and to the rostral and lateral portions of the pul- vinar. This vascular territory is known as the inferolateral territory.
(4) The territory of the posterior choroidal arteries. The poster- ior choroidal arteries also arise from the P2 portion of the posterior cerebral artery, and are comprised of a number of branches. These supply predominantly the lateral geni- culate nucleus, the inferolateral portion of the pulvinar and the lateral posterior (LP) nucleus and the lateral dorsal nucleus. Other branches may supply a portion of the med- ial geniculate and the posterior portions of the intralami- nar nuclei. This vascular territory is known as the posterior territory.
Variant territories
As if having to remember the four classical territories and names of the supplying arteries were not enough, there has been a recent addition to these in the form of variant terri- tories (see Carrere et al.,2004). The authors, in a major review of the Lausanne Stroke Registry, found that 30 percent of all thalamic stroke patients apparently do not know their vascu- lar anatomy. These patients presented with thalamic strokes that could not be easily classified into one of the four classical categories. An analysis of those patients led to a description of three variant vascular territories, hypothesized to be based either on variations in vascular supply or a watershed ischemia pattern:
(1) Anteromedian territory: infarcts here overlap the classical anterior and paramedian territories, usually combining the posterior part of the anterior territory with the anterior part of the paramedian territory.
(2) Central territory: infarcts here are in the center of the thala- mus, and thus in involve the adjacent parts of all four classical territories.
(3) Posterolateral territory: infarcts here overlap the classical inferolateral and posterior territories, usually involving the posterior part of the inferolateral territory with the anterior part of the posterior territory.
Summary
In summary, then, the thalamic nuclei seem to function in five domains: processing sensory information; participating in gen- eral motor functions and speech; affecting general arousal (the reticular and intralaminar nuclei are important here); partici- pating in high-level cognitive functions, such as judgment, rea- soning, memory and visuospatial processing (the association nuclei are important here); interacting with the limbic system to impact mood, affect, and motivation (the anterior thalamic nuclei are most important here). Various nuclei participate in each of these functions, and thalamic lesions, including infarcts, destroy these nuclei in varied combinations. Thus, clinicopathologic correlations can be difficult. However, using the neuroanatomic approach we have described, at least a mea- sure of order may be imposed on the chaos.
Probably the most important ‘‘take home’’ point of this chapter is that the thalamus is a complex structure with invol- vement in multiple brain systems. Most physicians outside the realm of neurology/neuroradiology associate only one sort of clinical presentation with thalamic lesions: contralat- eral sensory deficits. Hopefully, this chapter will illustrate that thalamic pathology provides a much richer and more complex spectrum of clinical abnormalities and clinicopathologic correlations.
With that, let’s take some cases!
Reference
Carrere, E., Michel, P., and Bogousslavsky, J. Anteromedian, central, and posterolateral infarcts of the thalamus: three variant types. Stroke 2004; 35: 2826.
Fig. 6.7. The arterial supply of the thalamus. Anterior nucleus (AN), reticular nucleus (R), ventral anterior nucleus (VA), ventral lateral nucleus (VLo/VLc), lateral dorsal nucleus (LD), dorsal medial nucleus (DM), lateral posterior nucleus (LP), ventral posterolateral nucleus (VPL), ventral posteromedial nucleus (VPM), centromedian nucleus (CM), intralaminar nuclei (Int).
Case 6.1
48-year-old female patient, who presented initially with ‘‘altered mental status’’ 7 days ago. Notable on the patient’s neurologic evaluation was abulia with diminished verbal output and hypo- phonia, mild left-sided weakness, a suggestion of left-sided hemineglect, and word-finding difficulties with perse- veration during speech. Comprehension and repetition were intact. No sensory deficit was elicited. Memory testing revealed decreased word recall as well as visual memory impairment. The patient also had constructional apraxia. The patient seemed disoriented in time, unable to sequence events properly during her hospital stay, overlapping events from last week onto events of today.
For non-neurologists, the above history may be a bit daunting. For example, what is abulia? What is hemineglect and how can we test for it? How can we test for visual, or visuospatial, memory impairment?
Gradually gaining familiarity with terms typically used by neu- rologists in describing patient findings is important for neuro- radiologists. The author has found that this knowledge accrues in bits and pieces. Therefore, here are a few bits. Abulia refers to apathy or lack of spontaneous action not accounted for by a decreased level of consciousness. Hemineglect is failure to respond to stimuli coming from one side of space, not accounted for by a motor or sensory deficit. Therefore, not responding to visual stimuli in the right visual field after a left occipital infarct does not count as hemineglect, because it is caused by a homo- nymous hemianopsia secondary to the stroke. The neglected side is opposite to the side of the responsible brain lesion. Briefly, hemineglect may be sensory (i.e., ignoring sensory stimuli to one side of the body or coming from one side of space), motor (lack of motor response in the affected half of space), or representational (being unable to properly generate mental images; half of the image is ignored). Hemineglect may also be personal (ignoring half of one’s body, such as not combing the hair on one side of the head) or spatial (ignoring half of the outside space, such as not eating the food on one half of a plate). Typical tests for hemine- glect include the line bisection test and cancellation tests. The line bisection test consists of drawing a line and asking the patient to divide it in half. If the patient ignores one-half of the line and proceeds to bisect only the half which he perceives, the mark will be off midline. Therefore, a patient with a right- sided brain lesion will have left hemineglect. He will ignore the left half of a horizontal line, and his bisection mark will be off midline toward the right. Cancellation tests involve such things as using a variety of figures scattered across a piece of paper and asking the patient to cross out one particular type, such as ‘‘stars.’’ The patient with left hemineglect will only cross out stars on the right half of the paper. Another test for representational hemi- neglect is to ask the patient to draw a clockface. If the patient neglects one half of the clock, or tries to bunch up all of the numbers on one semicircular arc, then this suggests hemineglect. An excellent reference on the topic of hemineglect is Plummer et al.,2003. Three common tests of memory are (a) the 15-word test, where the patient tries to recall 15 words read by the exam- iner, and may have multiple tries in which he learns the words; (b) Hebb’s audioverbal span test, where the patient repeats longer and longer series of numbers read by the examiner; and (c) Corsi blocks visuospatial memory test, where the patient must mimic the examiner by touching an increasing number of blocks in the right order. The well-known game Simon, with the flashing lights, is the commercial version of this test.
Speaking of memory impairment, it may appear that we have forgotten about our patient.Figure6.8shows an image from her MRI scan. What are the findings? What is your diagnosis?
Diagnosis
The scan shows abnormal hyperintensity in the anterior aspect of the right thalamus. The most likely diagnosis is an infarct, which this turned out to be.
In what thalamic vascular territory does the infarct lie? What structures are typically involved by infarcts in this territory? What is the typical clinical presentation for such infarcts?
This infarct is in the tuberothalamic artery territory, which sup- plies the anterior thalamus. A common synonym for this artery is the polar artery. This artery, once again, originates from the poster- ior communicating artery, whereas the remainder of the thalamic supply is from the posterior cerebral artery. The structures typically involved by infarcts in this territory are the anterior nucleus (ANT), the ventral anterior nucleus (VA), the rostral part of the ventral lateral nucleus (VL), the ventral part of the dorsomedial nucleus (DM), the mammillothalamic tract, and the anterior portion of the internal medullary lamina. The typical clinical findings are termed ‘‘neuropsychological’’ and consist of:
(a) Abulia. The patient may show apathy and lack of spontaneity. (b) Impairment of recent memory and new learning. This is thought to result from infarction of the mammillothalamic tracts, which connect the hippocampal formations to the anterior thalamic nuclei, as well as infarction of the anterior thalamic nuclei them- selves. Various reports suggest that visual memory is more involved in right-sided tuberothalamic strokes, whereas verbal memory is more affected in left-sided tuberothalamic strokes. (c) Hemineglect and visuospatial impairment. This is thought to be
more common in right tuberothalamic strokes.
(d) Dsyphasia. According to some, this is a milder form of aphasia. According to others, it is the same as aphasia, the difference
being that Americans say ‘‘aphasia’’ whereas Europeans say ‘‘dysphasia.’’ Anterior thalamic infarcts lead to a particular form of dysphasia, typified by word-finding difficulties, hypo- phonia, paraphasias and perseveration. Paraphasia is the pro- duction of unintended syllables or words during speech. It may involve saying only part of a word instead of the whole word or inverting part of a word (i.e., tevilision instead of television) – this is literal paraphasia. It may also involve word substitutions, such as saying one word when you mean your mother . . . er, when you mean another. This is verbal paraphasia. Typically, the dysphasia associated with anterior thalamic infarcts shows relatively preserved compre- hension and preserved repetition.
The conventional wisdom is that dysphasia is more com- mon with left-sided tuberothalamic infarcts whereas visuo- spatial deficits are more common with right-sided infarcts. However, a nice paper on anterior thalamic infarcts, repre- senting a fairly large series, failed to find this lateralization (see Ghika-Schmid and Bogousslavsky,2000).
(e) Disorientation to time and place. These infarcts may actually show a most interesting feature, in which patients superimpose
events that are unrelated in time upon each other, as if they had happened within the same temporal frame. This leads to a state of parallel expression of mental activities, each proceed- ing separately with the patient thinking that they all belong to the same time frame. This has been termed palipsychism by Ghika-Schmid and Bogousslavsky, from the Greek palin [again] and psyche [soul].
(f) Facial aprosody. Here, there is a hemifacial paresis only for emo- tional responses. In other words, the patient has decreased spontaneous facial expressions over one-half of the face in response to emotional stimuli, but no motor deficit if the patient intentionally tries to smile or frown.
References
Ghika-Schmid, F., and Bogousslavsky, J. The acute behavioral syndrome of anterior thalamic infarction: a prospective study of 12 cases. Annals of Neurology 2000; 48: 220–227.
Plummer, P., Morris, M. E., and Dunai, J Assessment of unilateral neglect. Physical Therapy 2003; 83(8): 732–740.
Case 6.2
63-year-old patient who initially presented with sudden onset altered mental status, characterized by decreased consciousness and confusion. The patient’s sensorium cleared the day post-ictus but the patient remained confused and became agitated. Clinical examination showed astrexis of the right arm as well as upward gaze palsy. The patient had some antegrade memory deficit and confabulation. The patient’s speech was hypophonic with reduced fluency but intact repetition.
Presented inFig.6.9is an image from the patient’s MRI scan. What are the findings? What is your diagnosis?
Diagnosis
There is a subacute infarct in the left paramedian thalamus, hyperintense on DWI. Paramedian infarcts are the second most common thalamic infarcts, following inferolateral territory infarcts.
What structures are typically involved in paramedian thalamic infarc- tion? What are the signs and symptoms of infarcts in this territory?
The paramedian artery, once again, arises from the P1 portion of the posterior cerebral artery and courses within the thalamus from ventromedial to dorsolateral. It supplies predominantly the dorsomedial nucleus, the intralaminar nuclei including the cen- tromedian nucleus, the midline nuclei, and variable portions of the internal medullary lamina.
Paramedian infarcts of the thalamus typically present with alterations in arousal and memory. There is decreased conscious- ness, which may last from minutes to days. After clearing of the sensorium, the presentation is similar to anterior (tuberothalamic) territory infarcts. There is often confusion, and sometimes apathy, while at other times there is aggressiveness and poor impulse control. There are memory deficits, with anterograde amnesia being the most prominent feature. This is often accompanied by confabulation. An interesting case has been reported where the memory deficit was predominantly autobiographical, with rela- tive preservation of memory for famous events and people. This was thought to be secondary to disconnection of frontal and tem- poral memory circuits. A dysphasia typified by decreased verbal fluency, hypophonia, and paraphasias with intact repetition is also often present. This has been called by some the ‘‘adynamic aphasia
of Guberman and Stuss,’’ based on their description of the findings (see Guberman and Stuss,1983).
Interestingly, most patients also have oculomotor abnormal- ities, with the most common being upward gaze palsy. Other reported abnormalities include a vertical ‘‘one-and-a-half,’’ as well as internuclear ophthalmoplegia and defects in lateral gaze which have been termed ‘‘pseudo-sixth nerve palsies.’’
Motor abnormalities are typically not pronounced, but mild hemiparesis as well as asterixis of the contralateral arm have been reported. Classically and importantly, there is typically no sensory deficit in these infarcts.
With paramedian infarcts, there does seem to be a left–right discrepancy in terms of dysphasia versus visuospatial deficits and hemineglect, with dysphasia more common in left-sided thala- mic infarcts and decreased visual memory and hemineglect more common with right-sided infarcts. This is illustrated by the case of a 53-year-old male who showed left-sided hemineglect follow- ing a right paramedian thalamic infarct (Fig. 6.10). The patient had no evidence of dysphasia and no sensory deficits.
In summary, then, the salient features of paramedian thalamic infarcts are: (1) decreased arousal; (2) memory deficits, particularly anterograde amnesia, along with confabulation; (3) neuropsycho- logical dysfunction characterized by confusion, apathy, and some- times poor impulse control, agitation, and aggression; (4) thalamic dysphasia, more prominent in left-sided lesions; (5) decreased visuospatial processing and possibly contralateral hemineglect, more common in right-sided lesions; (6) oculomotor abnormal- ities, with upward gaze palsy being the most frequent feature.
It must be noted that these associations are mostly phenomen- ological: they come from carefully examining patients with para- median thalamic infarcts and cataloguing their clinical findings. However, some putative links between symptoms and what we have discussed so far in regard to thalamic anatomy can be made. For example, there are two fiber systems key to learning and memory: the mammillothalamic tract and the amygdalofugal pathway. As already mentioned in the previous case discussion, the mammillothalamic tract connects the anterior nuclei of the thalamus with the hippocampal formations, at least partially explaining memory deficits with tuberothalamic infarcts. The amygdalofugal pathway links the medial portions of the dor- somedial thalamic nuclei with the limbic system and the frontal cortex. In particular, it connects the magnocellular portion of the dorsomedial nuclei with the basal forebrain, the amygadala and the orbitofrontal cortices. It is postulated that damage here leads both to memory deficits and emotional disturbances. This circuit may thus explain why, although both tuberothalamic and para- median infarcts manifest with memory deficits, paramedian infarcts seem to have a higher predilection for deficits in judg- ment and emotional control.
The alterations in consciousness typical of paramedian infarcts