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A chamber of secrets The neurology of the thalamus: lessons from acute stroke
  1. Rob Powell1,
  2. Tom Hughes2
  1. 1Department of Neurology, Morriston Hospital, Swansea, UK
  2. 2Department of Neurology, University Hospital of Wales, Cardiff, UK
  1. Correspondence to Dr Rob Powell, Department of Neurology, Morriston Hospital, Heol Maes Eglwys, Swansea SA6 6NL, UK; robert.powell{at}wales.nhs.uk

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Case history

A 66-year-old woman presented unrousable from sleep one Sunday morning, having been well the previous evening. She remained sleepy for several hours, opening her eyes to verbal commands but remaining vague and disorientated with difficulty forming sentences. A CT scan of the head was reported as normal. She improved during the day and was discharged after a brief admission.

Over the next 5 days, her husband reported that she was not herself. She had clear word-finding difficulty, more pronounced when speaking English rather than her native Dutch. She was unsteady and veered to the right when walking. She would sleep for long periods and had difficulty reading. At no time did she have neck pain.

On examination following readmission 24 h later, she was in sinus rhythm, normotensive, with normal heart sounds but no carotid bruits. She was orientated but sleepy. She had a subtle expressive dysphasia with word-finding difficulty. Her memory was grossly intact. The amplitude and velocity of vertical saccades was reduced. She had no weakness, sensory loss, or pyramidal signs in her limbs, but her gait was ataxic.

A CT scan of head (figure 1) showed low density in the medial left thalamus, consistent with an infarct. Routine blood tests, chest X-ray, 12-lead ECG and Doppler scan of the extracranial carotid and vertebral arteries were normal. A transthoracic echocardiogram found a patent foramen ovale, with right-to-left shunt.

Figure 1

CT head scan demonstrating a left paramedian thalamic infarct.

We prescribed antiplatelet therapy and a statin. She gradually improved but 3 months later still had occasional word finding difficulty and, by choice, has a short sleep in the afternoon.

We diagnosed a paramedian thalamic infarction, probably due to an embolus from a proximal embolic source. She subsequently underwent closure of her patent foramen ovale.

Thalamic structure and function—a ‘rule of 4’

The thalamus lies between the midbrain and forebrain. It is multifunctional, acting as a relay of sensory information between subcortical structures and the cerebral cortex. Its large number of back-projecting corticothalamic fibres suggests a role in processing this information. It is important in regulating arousal, sleep and wakefulness, as well as in motor control and memory via its connections to basal ganglia, cerebellum and hippocampus.

The thalamus has at least thirteen distinct nuclei or groups of nuclei. However, to make an anatomical diagnosis that is roughly right (rather than exactly wrong), it helps to picture the thalamus as having four regions. Each has its own artery, occlusion of which produces potentially recognisable constellations of deficits.

Table 1 outlines the ‘rule of 4’. Figure 2 shows the four principal thalamic functional regions—the anterior, lateral, medial and posterior nuclei. For obvious reasons, their main functions mirror those of the corresponding regions of the cortex to which they project.

Table 1

The four main thalamic regions along with their principal functions and arterial blood supply

  • The anterior nuclei are involved with language and memory function

  • The lateral nuclei are involved mainly with motor and sensory function

  • The medial nuclei are important for maintaining arousal and memory

  • The posterior (pulvinar) nuclei are involved mainly with visual function.

Figure 2

(A) Schematic view of thalamic blood supply and four functional regions. M, medial thalamic nuclei; A, anterior thalamic nuclei; L, lateral thalamic nuclei; P, posterio/pulvinar thalamic nuclei. (B) Schematic view of thalamic blood supply and typical deficits encountered following infarction of each region.

Anatomically, the medial nuclei represent the superior extension of the midbrain reticular activating system, explaining their important role in maintaining arousal and vigilance. They share a blood supply with midbrain nuclei, including the red nucleus and the rostral interstitial nucleus of the medial longitudinal fasciculus, hence the ataxia and ophthalmoplegia. Disruption of limbic connections (mamillothalamic and amygdalothalamic) may explain the memory impairment.

The posterior cerebral artery forms the parent arterial supply to all four functional regions.1

  • The anterior and anterior-medial thalamus (and the mamillothalamic tracts) are supplied by the polar artery (sometimes known as the tuberothalamic artery). This is absent in 40% of people, who therefore depend upon the paramedian thalamic arteries.2 ,3 If the polar artery is absent, dysphasia and a more pronounced amnesia form part of the syndrome of paramedian thalamic infarction.4

  • The lateral thalamus is supplied by the thalamogeniculate arteries (sometimes known as the inferolateral arteries).

  • The medial thalamic nuclei are supplied by the paramedian arteries. In a relatively common anatomical variant (described by Percheron), both paramedian thalamic arteries arise from the same side, either as a single trunk or as two separate but very closely related vessels, predisposing to bilateral paramedian thalamic infarction following unilateral vessel occlusion (figure 3).5 In some people, the paramedian thalamic arteries and the paramedian mesencephalic arteries to the midbrain originate from a common stem, occlusion of which produces more extensive infarction.

  • The posterior thalamus is supplied by the posterior choroidal arteries.

Figure 3

Variations in the paramedian arteries. Types IIa and IIb are those associated with bilateral paramedian thalamic infarction (taken from Reilly et al1).

Further cases: clinical features

The case above is interesting and anomalous in several ways. The combination of dysphasia, ataxia and ophthalmoplegia is not readily explained by a single lesion, particularly in the emergency unit. Furthermore, the case seems to contradict two popular maxims of stroke neurology: that stroke does not cause loss of consciousness, and that posterior circulation strokes do not cause dysphasia.

During regular case presentations at the teleconferenced All-Wales Stroke Meeting, we collected a further 9 patients whose imaging showed ischaemic or haemorrhagic thalamic lesions, of arterial or venous origin (figure 4). Table 2 summarises their clinical details.

Table 2

Clinical and imaging features of nine further cases

Figure 4

(A) CT scan of head showing haemorrhage in the anterior left thalamus, and high density in the internal cerebral veins and straight sinus, consistent with venous thrombosis. (B) Axial FLAIR MRI showing bilateral paramedian infarcts. (C) T2-weighted MRI scan demonstrating bilateral paramedian thalamic infarcts and left thalamic haemorrhage. (D) CT head demonstrating an infarct in the left lateral thalamus. FLAIR, fluid attenuated inversion recovery.

We were struck by the highly variable presentations, including dysphasia, mutism, hemiparesis, transient loss of consciousness (with seizure-like features), diplopia and clinically obvious cognitive deficits. In general, however, each case conformed to the ‘Rule of 4’. Of note, there were two cases of thalamic haemorrhage—into areas of venous infarction secondary to straight sinus thrombosis—giving symptoms of raised intracranial pressure. In several cases, reduced vigilance immediately following the initial symptoms was a valuable clue to a thalamic problem.

Reduced vigilance was the most common feature (figure 5), seen in eight cases, and in those with paramedian or bilateral infarctions. The high number of cases with dysphasia presumably reflects the disproportionate number of dominant hemisphere lesions. At the time of writing, four patients have residual cognitive deficits. The pattern of these, with cognitive slowing, apathy and concentration difficulty, is more in keeping with a ‘subcortical’ picture; interestingly, all four had bilateral infarctions.

Figure 5

Range of clinical features seen in our series of patients with thalamic lesions.

Of the 10 cases, 7 were infarcts and 3 were haemorrhages. Two were venous in origin and the remainder arterial. Interestingly, six had no recognised vascular risk factors.

Previous reports

Reilly et al1 described six cases with bilateral paramedian infarctions. All had impaired vigilance, ranging from coma to intermittent hypersomnolence. However, in all these (as with ours), the impaired vigilance was transient. There was a range of oculomotor disorders (including impaired convergence, bilateral third nerve palsies, lid retraction and pupillary abnormalities); all six had vertical gaze paresis, which did not always fully resolve. The likely anatomical basis for this was the rostral interstitial nucleus of the medial longitudinal fasciculus, also supplied by the paramedian artery. One unusual feature, seen in two patients and also in our cases, was transient diplopia preceding an episode of hypersomnolence. Two patients suffered significant permanent cognitive difficulty; only three had traditional vascular risk factors.

In a review of the vascular syndromes affecting the thalamus, Schmahman concluded that clinical presentations of thalamic stroke fall into four principal vascular syndromes, but that variability in arterial territories and thalamic anatomy gives variation within each of these.6 These syndromes closely correspond to the functional classification suggested above.

  • Polar artery territory strokes resulted in fluctuating arousal and orientation, with impaired learning and memory. Left-sided polar artery lesions caused expressive dysphasia, with reduced verbal fluency and naming ability; right-sided polar artery lesions caused hemispatial neglect. Emotional facial paresis was also reported.

  • Paramedian artery territory strokes produced neuropsychological disturbances predominantly in arousal and memory. Reduced arousal tended to be fluctuating and transient when the infarction was unilateral but patients with bilateral lesions were more severely affected, and the amnesia could be dense (retrograde and anterograde) and persistent, similar to that seen in the Korsakoff's syndrome. Gaze palsies commonly accompanied lesions involving the midbrain nuclei.

  • Thalamogeniculate artery territory strokes caused lateral thalamic infarctions and sensory and motor disturbances (including thalamic pain syndromes and ataxic hemiparesis) but rarely language or other neuropsychological deficits.

  • Posterior choroidal artery territory strokes affected the pulvinar and geniculate nuclei, usually causing visual field and sensory deficits, although sometimes caused hyperkinetic movement disorders, including tremor and dystonia.

Another series reported three variant topographical patterns of thalamic infarction with distinct manifestations and aetiologies. These cases tended to have more extensive infarcts affecting two or more of the classical vascular territories and with more extensive clinical deficits, probably resulting from variation in thalamic arterial supply.7

Thalamic lesions may cause behavioural changes in particular patterns. These can mimic cortical behavioural syndromes, providing further evidence that the thalamus does more than simply relay motor and sensory information. Again, these patterns delineate on the basis of the four main arterial thalamic territories.

  • The anterior pattern consists mainly of thought perseverations, disorganised speech with superimposed unrelated information, apathy and amnesia.

  • Paramedian infarcts cause disinhibition syndromes, personality changes, loss of self-activation, amnesia, and, with extensive lesions, ‘thalamic dementia’, often difficult to distinguish from primary psychiatric disorders.

  • Inferolateral lesions and posterior lesions less commonly cause behavioural changes (executive dysfunction may develop).8

Severe ‘diencephalic’ anterograde amnesia is widely reported to follow lesions of the anterior and medial thalamic nuclei lesions or of their afferent white matter bundle, the mamillothalamic tract.9 Van der Werf et al. noted that damage to other structures, such as hippocampal and cortical atrophy and small vessel cerebrovascular disease, frequently accompanied thalamic infarcts, complicating the interpretation of memory, executive function and attention. Their lesion-overlap study, however, showed that in patients with ‘pure’ thalamic lesions, the amnesic syndrome—relatively sparing intellectual capacity and short-term memory—corresponded to lesions of the mamillothalamic tract.10

Advanced neuroimaging techniques, including perfusion CT, MRI tractography and high-resolution MRI, will most likely provide more detailed information about thalamic anatomy and connections. Correlations between disrupted thalamocortical connections and clinical findings may provide further insights into the functional roles of different thalamic nuclei.

Hypersomnia has been thought to result from disruption of sleep-generating and arousal-maintaining mechanisms in the thalamus. One group studied the evolution of neurological and neuropsychological problems following paramedian infarction.11 Some patients also underwent interval polysomnography to study the effect of paramedian thalamic infarction on the sleep–wake cycle. They found that hypersomnia improved markedly over the 1st year following stroke, with sleep needs returning almost to normal in those with unilateral infarcts. There was also a lesser increase in sleep requirement in those who had bilateral infarcts. Polysomnography showed changes in sleep architecture, with reduced sleep spindles, reduced proportion of stage 2 sleep and increased proportion of stage 1 sleep. The EEG changes did not reflect the clinical improvement and tended to persist. As in our patients, they found that the prognosis was worse in those with bilateral lesions, and better following right-sided infarcts.

Conclusions and clinical implications

These cases represent a challenge to acute stroke services, particularly as diagnostic changes in the thalamus are difficult to detect during the time window for thrombolysis. Ambulance clinicians are unlikely to consider the triage screening tests for patients with stroke (FAST, ROSIER) as relevant to patients presenting with thalamic lesions. Even if they were done, these crude screening tools are unlikely to be ‘positive’ because impaired vigilance and abnormal eye movements are more common than ‘scoring signs’ in the face and arm. Furthermore, the absence of traditional risk factors for stroke in a patient with an impaired consciousness is unlikely to put thalamic stroke at the top of the list of differential diagnoses in the emergency department.

Even when clinicians do consider the diagnosis, the differential diagnosis is wider than for ‘typical’ stroke, and could include hypoxia, hypercapnia, sepsis, drug overdose, Wernicke's encephalopathy, myasthenia gravis, Miller Fisher syndrome, botulism, viral encephalitis and structural and neoplastic disease of the brainstem. Prompt action required to investigate more treatable conditions may include checking plasma glucose, routine bloods, a blood gas, toxin screen, and giving intravenous thiamine. Often the first CT scan is normal, and a lumbar puncture may be required to exclude meningitis or encephalitis.

However, given the severity of the disability following a thalamic infarct, clinicians involved in stroke thrombolysis services must be aware of the clinical manifestations of ischaemia in this important structure, to improve patients’ chances of receiving thrombolysis. Stroke physicians must have a knowledge of the common presentations of thalamic stroke, as they need a high index of suspicion to make the diagnosis and to consider MRI with diffusion-weighted imaging as the imaging modality of choice. Even without these, however, the recognition of the localising significance of these very sudden onset clinical features may enable thrombolysis to be considered, despite initial normal investigations.

We suggest thinking of the thalamus in terms of four functional regions to help understand these presentations. In particular, the characteristic stroke syndrome of paramedian thalamic infarction is probably underdiagnosed; it is interesting in that it proves an exception to two widely held views that stroke is not a cause of loss of consciousness, and that posterior circulation strokes do not cause dysphasia. We also recommend considering the possibility of a straight sinus thrombosis as an underlying cause of thalamic haemorrhage, although without more advanced imaging (CT or MR venography) it is probably not possible on clinical grounds to distinguish venous infarction secondary to a straight sinus thrombosis from arterial ischaemia.

Thalamic disease mimics several different neurological conditions and should be considered in patients with an unusual collection of deficits, difficult to explain by a single lesion, in particular where there is impaired vigilance.

Acknowledgments

The authors thank Dr Maggie Hourihan, Dr Yogish Joshi, Dr Chris Hudson, Dr Robin Corkill, Dr Mark Wardle, Dr Bella Richard, Dr Sarah Woollard and Dr Trevor Pickersgill. All cases were originally presented in the teleconferenced All-Wales Stroke Meeting.

References

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Footnotes

  • Contributors Both authors contributed equally to the preparation of this manuscript.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed. This paper was reviewed by Adam Zeman, Exeter, UK.

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