Chapter 027. Aphasia, Memory Loss, and Other Focal Cerebral Disorders (Part 14) Caring for the Patient with Deficits of Higher Cerebral Function Some of the deficits described in this chapter are so complex that they may bewilder not only the patient and family but also the physician. It is imperative to carry out a systematic clinical evaluation in order to characterize the nature of the deficits and explain them in lay terms to the patient and family. Such an explanation can allay at least some of the anxieties, address the mistaken impression that the deficit (e.g., social disinhibition or inability to recognize family members) is psychologically motivated, and lead to practical suggestions for daily living activities. The consultation of a skilled neuropsychologist may aid in the formulation of diagnosis and management. Patients with simultanagnosia, for example, may benefit from the counterintuitive instruction to stand back when they cannot find an item so that a greater search area falls within the immediate field of gaze. Some patients with frontal lobe disease can be extremely irritable and abusive to spouses and yet display all the appropriate social graces during the visit to the medical office. In such cases, the history may be more important than the bedside examination in charting a course of treatment. Reactive depression is common in patients with higher cerebral dysfunction and should be treated. These patients may be sensitive to the usual doses of antidepressants or anxiolytics and deserve a careful titration of dosage. Brain damage may cause a dissociation between feeling states and their expression, so that a patient who may superficially appear jocular could still be suffering from an underlying depression that deserves to be treated. In many cases, agitation may be controlled with reassurance. In other cases, treatment with sedating antidepressants may become necessary. The use of neuroleptics for the control of agitation should be reserved for refractory cases since extrapyramidal side effects are frequent in patients with coexisting brain damage. Spontaneous improvement of cognitive deficits due to acute neurologic lesions is common. It is most rapid in the first few weeks but may continue for up to 2 years, especially in young individuals with single brain lesions. The mechanisms for this recovery are incompletely understood. Some of the initial deficits appear to arise from remote dysfunction (diaschisis) in parts of the brain that are interconnected with the site of initial injury. Improvement in these patients may reflect, at least in part, a normalization of the remote dysfunction. Other mechanisms may involve functional reorganization in surviving neurons adjacent to the injury or the compensatory use of homologous structures, e.g., the right superior temporal gyrus with recovery from Wernicke's aphasia. In some patients with large lesions involving Broca's and Wernicke's areas, only Wernicke's area may show contralateral compensatory reorganization (or bilateral functionality), giving rise to a situation where a lesion that should have caused a global aphasia becomes associated with a residual Broca's aphasia. Prognosis for recovery from aphasia is best when Wernicke's area is spared. Cognitive rehabilitation procedures have been used in the treatment of higher cortical deficits. There are few controlled studies, but some do show a benefit of rehabilitation in the recovery from hemispatial neglect and aphasia. Some types of deficits may be more prone to recovery than others. For example, patients with nonfluent aphasias are more likely to benefit from speech therapy than patients with fluent aphasias and comprehension deficits. In general, lesions that lead to a denial of illness (e.g., anosognosia) are associated with cognitive deficits that are more resistant to rehabilitation. The recovery from higher cortical dysfunction is rarely complete. Periodic neuropsychological assessment is necessary for quantifying the pace of the improvement and for generating specific recommendations for cognitive rehabilitation, modifications in the home environment, and the timetable for returning to school or work. In general medical practice, most patients with deficits in higher cognitive functions will be suffering from dementia. There is a mistaken belief that dementias are anatomically diffuse and that they cause global cognitive impairments. This is only true at the terminal stages. During most of the clinical course, dementias are exquisitely selective with respect to anatomy and cognitive pattern. Alzheimer's disease, for example, causes the greatest destruction in medial temporal areas belonging to the memory network and is clinically characterized by a correspondingly severe amnesia. There are other dementias where memory is intact. Frontal lobe dementia results from a selective degeneration of the frontal lobe and leads to a gradual dissolution of behavior and complex attention. Primary progressive aphasia is characterized by a gradual atrophy of the left perisylvian language network and leads to a progressive dissolution of language that can remain isolated for up to 10 years. An enlightened approach to the differential diagnosis and treatment of these patients requires an understanding of the principles that link neural networks to higher cerebral functions. FURTHER READINGS Catani M, Ffychte H: The rises and falls of disconnection syndromes. Brain 128:2224, 2005 [PMID: 16141282] Cruts M et al: Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature 442:916, 2006 Gitelman DR et al: A large-scale distributed network for covert spatial attention. Further anatomical delineation based on stringent behavioral and cognitive controls. Brain 122:1093, 1999 [PMID: 10356062] Heiss W-D et al: Differential capacity of left and right hemispheric areas for compensation of poststroke aphasia. Ann Neurol 45:430, 1999 [PMID: 10211466] Hillis AE: Aphasia: Progress in the last quarter of a century. Neurology 69:200, 2007 [PMID: 17620554] Knibb JA et al: Clinical and pathological characterization of progressive aphasia. Ann Neurol 59:156, 2006 [PMID: 16374817] Leiguarda RC, Marsden CD: Limb apraxias: Higher-order disorders of sensorimotor integration. Brain 123:860, 2000 [PMID: 10775533] Li X et al: Prion protein codon 129 genotype is altered in primary progressive aphasia. Ann Neurol 58:858, 2005 [PMID: 16315279] Mesulam M-M: Behavioral neuroanatomy: Large-scale networks, association cortex, frontal syndromes, the limbic system and hemispheric specializations, in Principles of Behavioral and Cognitive Neurology, 2d ed, M-M Mesulam (ed). New York, Oxford University Press, 2000, pp 1–120 ———: Current concepts: Primary progressive aphasia—a language-based dementia. New Engl J Med 348:1535, 2003 ———: The human frontal lobes: Transcending the default mode through contingent encoding, in Principles of Frontal Lobe Function, DT Stuss, RT Knight (eds). New York, Oxford University Press, 2002, pp 8–30 Summerfield JJ et al: Orienting attention based on long-term memory experience. Neuron 49:905, 2006 [PMID: 16543137] BIBLIOGRAPHY Damasio AR, Damasio H: Aphasia and the neural basis of language, in Principles of Behavioral and Cognitive Neurology, 2d ed; M-M Mesulam (ed). New York, Oxford University Press, 2000, pp 294–315 Deuel RK, Collins RC: Recovery from unilateral neglect. Exp Neurol 81:733, 1983 [PMID: 6884482] Geschwind N: Disconnection syndromes in animals and man. Brain 88:237, 1965 [PMID: 5318481] Grensham GE et al: Post-Stroke Rehabilitation. U.S. Department of Health and Human Services Agency for Health Care Policy and Research, Publication No. 95-0662. Rockville, Maryland, 1995 Heilman KM et al: Neglect and related disorders, in Clinical Neuropsychology, KM Heilman, E Valenstein (eds). New York, Oxford University Press, 1985, pp 279–336 Markowitsch HJ: Memory and amnesias, in Principles of Behavioral and Cognitive Neurology, 2d ed, M-M Mesulam (ed). New York, Oxford University Press, 2000 Mesulam M-M: From sensation to cognition. Brain 121:1031, 1998 ———: Higher visual functions of the cerebral cortex and their disruption in clinical practice, in Principles and Practice of Ophthalmology, 2d ed, DM Albert, FA Jakobiec (eds). Philadelphia, Saunders, 1999 ———: Primary progressive aphasia. Ann Neurol 49:425, 2001 ———: Spatial attention and neglect: Parietal, frontal and cingulate contributions to the mental representation and attentional targeting of salient extrapersonal events. Phil Trans R Soc Lond B 354:1325, 1999 Mohr JR et al: Broca's aphasia: Pathologic and clinical. Neurology 28:311, 1978 [PMID: 565019] Naeser MA, Helm-Estabrooks N: CT scan lesion localization and response to melodic intonation therapy with nonfluent aphasia cases. Cortex 21:203, 1985 [PMID: 4028738] Price BH et al: Neuropsychological patterns and language deficits in 20 consecutive cases of autopsy-confirmed Alzheimer's disease. Arch Neurol 50:931, 1993 [PMID: 8363447] Ross ED: Affective prosody and aprosodias, in Principles of Behavioral and Cognitive Neurology, 2d ed, M-M Mesulam (ed). New York, Oxford University Press, 2000 Turner RS et al: Clinical, neuroimaging, and pathologic features of progressive nonfluent aphasia. Ann Neurol 39:166, 1996 [PMID: 8967747] Weiller C et al: Recovery from Wernicke's aphasia: A positron emission tomographic study. Ann Neurol 37:723, 1995 [PMID: 7778845] Weintraub S: Neuropsychological assessment of mental state, in Principles of Behavioral and Cognitive Neurology, 2d ed, M-M Mesulam (ed). New York, Oxford University Press, 2000 . Chapter 027. Aphasia, Memory Loss, and Other Focal Cerebral Disorders (Part 14) Caring for the Patient with Deficits of Higher Cerebral Function Some of the deficits described in this chapter. medial temporal areas belonging to the memory network and is clinically characterized by a correspondingly severe amnesia. There are other dementias where memory is intact. Frontal lobe dementia. diagnosis and treatment of these patients requires an understanding of the principles that link neural networks to higher cerebral functions. FURTHER READINGS Catani M, Ffychte H: The rises and