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Keywords:

  • intralaminar thalamic nucleus;
  • progressive supranuclear palsy;
  • psychiatric symptoms;
  • stupor-like state

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. CASE REPORTS
  5. DISCUSSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES

Four patients with progressive supranuclear palsy presented with various psychiatric symptoms. Periodic stupor-like states due to fluctuations of consciousness were observed in all four cases. Magnetic resonance imaging showed severe dilatation of the third ventricle suggesting atrophy of the thalami. Neuropathological examination in one of the cases confirmed severe fibrillary gliosis in the intralaminar thalamic nucleus. So far, few studies have focused on periodic stupor-like states observed in progressive supranuclear palsy patients. From our cases and from the literature, we postulate that the lesions in the intralaminar thalamic nuclei may have close relevance to the stupor-like states seen in progressive supranuclear palsy patients.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. CASE REPORTS
  5. DISCUSSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES

Progressive supranuclear palsy (PSP), first described in 1964 by Steele et al.,1 is a neurodegenerative disorder characterized by extrapyramidal signs and pseudobulbar palsy. Patients present with gait disturbance, dysphagia, nuchal dystonia and ophthalmoplegia mainly affecting vertical gaze.1,2 Various psychiatric symptoms such as subcortical dementia, affective changes and psychotic symptoms have also been described.2–7 However, there are very few reports dealing with periodic stupor-like states.8,9 Here we report four patients with PSP who showed fluctuations of consciousness that resulted in periodic stupor-like states. Magnetic resonance imaging (MRI) was done in three of the living cases, which showed severe dilatation of the third ventricle suggesting atrophy of the thalami. The fourth case was an autopsy case in which severe fibrillary gliosis was detected in the intralaminar thalamic nucleus. We discuss the relevance between the thalamic lesions and the psychiatric symptoms observed in our cases.

CASE REPORTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. CASE REPORTS
  5. DISCUSSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES

Case 1

An 83-year-old woman became hypochondriac and gradually became depressive and forgetful. Visual hallucination, insomnia and delirium occurred. Use of antipsychotics and antidepressants did not improve the symptoms. Gait disturbance, incontinence, edema, tachycardia and pseudobulbar palsy were observed. While in the hospital, she frequently became unresponsive to external stimuli with an abnormality of muscle tone in which arms and legs were held in a rigid posture. She recovered from such stupor-like states in a day or two, being alert enough to talk to others. The severity of psychiatric symptoms changed every few days. The brain MRI (Fig. 1) revealed severe dilatation of the third ventricle. She eventually fell into akinetic mutism.

image

Figure 1. Coronal T1-weighted magnetic resonance imaging shows severe dilatation of the third ventricle.

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Case 2

A 73 year-old man became hypochondriac and complained about stomach problems. Antidepressants did not improve his complaints. He developed akinesia, weakness of the hands and a masked face. He had frequent falls. The patient was often seen staring blankly at a point. He was admitted to our hospital at the age of 75. The brain MRI (Fig. 2A–C) showed severe dilatation of the third ventricle with atrophy of the brain stem and diencephalon. T2-weighted images showed high intensity signals bilaterally in the pons, thalamus and caudate nucleus.

image

Figure 2. T2-weighted magnetic resonance imaging shows high-intensity signals bilaterally in the pons, thalamus and caudate nucleus (a). Severe dilatation of the third ventricle is seen on the coronal section (b).

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Case 3

A 65 year-old man was seen with a forward bending posture and a masked face. He began to have frequent falls. Dementia became apparent at the age of 70. He spoke less and communicated by writing. He was admitted to our hospital due to dysphagia and tube feeding was started on admission. Abnormal behaviors, such as pulling out the feeding tube, were often seen. Neurological examination showed limited vertical movement of the eyes, loss of postural reflex and rigidity of the trunk. The brain MRI (Fig. 3) showed severe dilatation of the third ventricle. A distinct fluctuation of consciousness level was observed. He often became unresponsive in a rigid posture, but was also seen talking and reading newspapers between those stupor-like episodes.

image

Figure 3. Coronal T1-weighted magnetic resonance imaging shows severe dilatation of the third ventricle.

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Case 4

A 67 year-old man was suffering from a gait disturbance and mental deterioration.10 Neurological examination at the age of 71 revealed pseudobulbar palsy, horizontal ophthalmoplegia and truncal dystonia. Mental deterioration, including forgetfulness and character change was also noted, and the patient sometimes exhibited periodic stupor-like states. He died of bronchopneumonia at the age of 71. Neuropathological examination confirmed typical pathological changes of PSP, such as neuronal loss, neurofibrillary tangles, and fibrillary gliosis in the subcortical nuclei. Severe fibrillary gliosis was detected in the intralaminar thalamic nucleus (Fig. 4).

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Figure 4. Fibrillary gliosis was observed by Holzer staining. Coronal section of the right cerebrum shows localized fibrillary gliosis in the thalamus (a). Close inspection of the left thalamus reveals a highly damaged area in the intralaminar thalamic nucleus (b).

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DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. CASE REPORTS
  5. DISCUSSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES

Psychiatric symptoms are a frequent finding in patients with PSP, however, not many studies in the literature have focused on this topic. The most common psychiatric finding is dementia, apparent in 52–89% of the PSP patients.3,4,7 Affective disturbances often present as apathy or depressive states,4–6 as in cases 1 and 2. Hallucination and delusion, as seen in case 1, are more infrequent, reported in 0–16% of cases.5,6

Our cases presented with periodic stupor-like states during the course of PSP. There have not been many reports regarding stupor-like states in PSP patients. In 1991 Amano et al. reported six autopsy cases of PSP in which three cases presented periodic stupor-like states leading to akinetic mutism in the last stage.8 These patients suddenly fell into a stupor-like state and recovered spontaneously within a few minutes to a few hours. They were akinetic and unresponsive during the stupor-like states, often seemingly staring blankly at a point. In 1997, Amano reported more autopsy cases of PSP,9 in which six out of 13 cases presented with periodic stupor-like states.

Cases 1, 2 and 3 showed severe dilatation of the third ventricle on MRI suggesting atrophy of the bilateral thalami. PSP is usually characterized by brainstem and basal ganglia degeneration but severe lesions are also often found in the thalamus. Amano et al. have investigated neuropathological changes of the thalamus observed in PSP patients presenting periodic stupor-like states,8 revealing neurofibrillary tangles, fibrillary gliosis and neuronal loss in the thalamus. The Holzer staining of the thalamus in case 4 shows fibrillary gliosis in the intralaminar thalamic nucleus. Although similar neuropathological findings have been reported previously,8,9 an image of the thalamus with clearly observable lesions in the intralaminar thalamic nucleus (Fig. 4) is rare. The lesions observed in this specimen are consistent with the report by Henderson et al. in which a dramatic reduction was observed in the total neuronal number in the caudal intralaminar thalamic nuclei in PSP cases.11 These facts suggest that the degeneration of the intralaminar thalamic nuclei has caused the thalamic atrophy observed in our cases.

To our knowledge, there have been no studies in literature discussing the symptoms caused by the lesions in the intralaminar thalamic nuclei in PSP patients. However, there are several studies on thalamic infarctions suggesting that intralaminar nuclei lesions may cause various psychiatric symptoms. Werf et al. reported a patient with a lacunar infarction circumscribed to the region of the dorsal caudal intralaminar nuclei of the right thalamus who presented with apathy,12 lethargy, slowness, lack of concentration, and memory deficits. Other studies on thalamic infarctions involving intralaminar nuclei report various psychiatric symptoms such as personality changes, memory deficits, attention deficits and loss of affection.13,14 Cases of glioma with psychiatric symptoms related to thalamic lesions have also been reported in which the bilateral glioma of the dorsomedial and intralaminar nuclei of the thalamus displayed personality changes and/or mental deterioration, including memory loss, inattention, confusion, hallucination, hyperphagia or slow mentation.15 A case of bithalamic infarction, particularly involving the intralaminar thalamic nuclei, which resulted in akinetic mutism,16 suggests that severe intralaminar nuclei lesions can cause akinetic mutism. These findings suggest that major psychiatric symptoms in PSP patients may have a close relationship with the lesions in the intralaminar thalamic nuclei.

The intralaminar thalamic nuclei are the sites of termination for the ascending reticular activating system. The intralaminar neurons project cholinergic fibers diffusely to the striatum and cerebrum providing generalized activation. This widespread connectivity acts as an attention-action coordinator. It is surmised that the alteration of the connectivity between intralaminar thalamic nuclei and prefrontal and anterior cingulate cortices would cause a vegetative state in human beings.17 Specifically, the posterior centromedian-parafascicular complex (CM-Pf) may be involved in motivational responses.18 A disturbance of its function may result in severe apathy, and more severe lesions will interfere with consciousness. If the lesions in the intralaminar thalamic nuclei occur bilaterally, it engenders unresponsiveness.19 It is possible that the loss of neurons in the intralaminar thalamic nuclei of PSP patients resulted in alteration of consciousness, which presented as stupor-like states.

It is interesting to note that the stupor-like states present episodically and the patients remain alert between episodes. Neurodegenerative diseases are usually characterized by chronic progression, and fluctuations of symptoms are not often observed. It appears to be that the function of the intralaminar thalamic nuclei is periodically disturbed in PSP patients at some time during the course of degeneration. As the degeneration progresses, the intralaminar nuclei become completely impaired resulting in akinetic mutism.

In conclusion, fluctuations of consciousness presenting as periodic stupor-like states may be seen in PSP patients. Lesions have been found in the intralaminar nuclei of the thalamus, the function of which is necessary to maintain consciousness. The correlation between neuropathological changes in the intralaminar thalamic nuclei and the fluctuation of consciousness is strongly suggested.

ACKNOWLEDGMENTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. CASE REPORTS
  5. DISCUSSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES

The content of this manuscript were presented at the 20th Annual meeting of Japanese Psychogeriatric Society.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. CASE REPORTS
  5. DISCUSSION
  6. ACKNOWLEDGMENTS
  7. REFERENCES
  • 1
    Steele JC, Richardson JC, Olszewski J. Progressive Supranuclear Palsy. A heterogeneous degeneration involving the brain stem, basal ganglia and cerebellum with vertical gaze and pseudobulbar palsy, nuchal dystonia and dementia. J Arch Neurol 1964; 10: 333359.
  • 2
    Nath U, Ben-Shlomo Y, Thomson RG, Lees AJ, Burn DJ. Clinical features and natural history of progressive supranuclear palsy: a clinical cohort study. Neurology 2003; 60: 910916.
  • 3
    Menza MA, Cocchiola J, Golbe LI. Psychiatric symptoms in progressive supranuclear palsy. Psychosomatics 1995; 36: 550554.
  • 4
    Chiu HF. Psychiatric aspects of progressive supranuclear palsy. Gen Hosp Psychiatry 1995; 17: 135143.
  • 5
    Lauterbach EC. The neuropsychiatry of Parkinson's disease and related disorders. Psychiatr Clin North Am 2004; 27: 801825.
  • 6
    Litvan I, Cummings JL, Mega M. Neuropsychiatric features of corticobasal degeneration. J Neurol Neurosurg Psychiatry 1998; 65: 717721.
  • 7
    Aarsland D, Litvan I, Salmon D, Galasko D, Wentzel-Larsen T, Larsen JP. Performance on the dementia rating scale in Parkinson's disease with dementia and dementia with Lewy bodies: comparison with progressive supranuclear palsy and Alzheimer's disease. J Neurol Neurosurg Psychiatry 2003; 74: 12151220.
  • 8
    Amano N, Nagatomo H, Yokoi S, Yagishita S, Saitoh A, Mizutani T. [The thalamic changes in progressive supranuclear palsy.] No To Shinkei 1992; 44: 421428. (In Japanese.)
  • 9
    Amano N. Progressive Supranuclear Palsy, Encyclopedia of Clinical Psychiatry (Japanese). Tokyo, Japan: Nakayama Shoten-Publishing Co, 1997; 160176.
  • 10
    Hanihara T, Kubota H, Amano N, Yamaoka K, Yagishita S. [Widespread argentophilic structures in progressive supranuclear palsy–an autopsy case report.] No To Shinkei 1994; 46: 487492. (In Japanese.)
  • 11
    Henderson JM, Carpenter K, Cartwright H, Halliday GM. Loss of thalamic intralaminar nuclei in progressive supranuclear palsy and Parkinson's disease: clinical and therapeutic implications. Brain 2000; 123: 14101421.
  • 12
    Van Der Werf YD, Weerts JG, Jolles J, Witter MP, Lindeboom J, Scheltens P. Neuropsychological correlates of a right unilateral lacunar thalamic infarction. J Neurol Neurosurg Psychiatry 1999; 66: 3642.
  • 13
    Bogousslavsky J, Ferrazzini M, Regli F, Assal G, Tanabe H, Delaloye-Bischof A. Manic delirium and frontal–like syndrome with paramedian infarction of the right thalamus. J Neurol Neurosurg Psychiatry 1988; 51: 116119.
  • 14
    Mennemeier M, Fennell E, Valenstein E, Heilman KM. Contributions of the left intralaminar and medial thalamic nuclei to memory. Comparisons and report of a case. Arch Neurol 1992; 49: 10501058.
  • 15
    Partlow GD, Del Carpio-O'Donovan R, Melanson D, Peters TM. Bilateral thalamic glioma: review of eight cases with personality change and mental deterioration. AJNR Am J Neuroradiol 1992; 13: 12251230.
  • 16
    Van Domburg PH, Ten Donkelaar HJ, Notermans SL. Akinetic mutism with bithalamic infarction. Neurophysiological correlates. J Neurol Sci 1996; 139: 5865.
  • 17
    Laureys S, Faymonville ME, Luxen A, Lamy M, Franck G, Maquet P. Restoration of thalamocortical connectivity after recovery from persistent vegetative state. Lancet 2000; 355: 17901791.
  • 18
    Henderson JM, Schleimer SB, Allbutt H et al. Behavioural effects of parafascicular thalamic lesions in an animal model of parkinsonism. Behav Brain Res 2005; 162: 222232.
  • 19
    Bogen JE. Some neurophysiologic aspects of consciousness. Semin Neurol 1997; 17: 95103.