Dynamic aphasia as an early sign of corticobasal degeneration: Clinico-radio-pathological correlation.

A 72-year-old man presented with a 6-month history of decreased voluntary speech. Sparse speech and decreased word fluency were observed. Articulation, naming, comprehension, and repetition were preserved. Agrammatism and paraphasia were not observed. These characteristics matched those reported as dynamic aphasia. Other findings were mild behavioral symptoms, recent memory impairment, and right hemiparkinsonism. The patient's voluntary speech continued to reduce and behavioral symptoms progressed. Brain MRI including voxel-based morphometric analysis showed left-dominant white matter volume reduction in the frontal lobe including those between the left supplementary motor area (SMA)/preSMA and the frontal operculum, likely involving the frontal aslant tract (FAT). The patient became completely mute after two years from disease onset and died of aspiration pneumonia. The neuropathological diagnosis was corticobasal degeneration (CBD). This case suggests that dynamic aphasia may be the initial sign of CBD and that early involvement of left FAT may be responsible for this feature.

High sensitivity of asymmetric 18F-THK5351 PET abnormality in patients with corticobasal syndrome.

Corticobasal syndrome (CBS) is characterized by symptoms related to the asymmetric involvement of the cerebral cortex and basal ganglia. However, early detection of asymmetric imaging abnormalities can be challenging. Previous studies reported asymmetric 18F-THK5351 PET abnormalities in CBS patients, but the sensitivity for detecting such abnormalities in larger patient samples, including early-stage cases, remains unclear. Patients clinically diagnosed with CBS were recruited. All patients displayed asymmetric symptoms in the cerebral cortex and basal ganglia. Asymmetric THK5351 PET abnormalities were determined through visual assessment. Brain MRI, perfusion SPECT, and dopamine transporter (DAT) SPECT results were retrospectively reviewed. The 15 patients had a median age of 72 years (59-86 years) and a disease duration of 2 years (0.5-7 years). Four patients met the probable and 11 met the possible CBS criteria according to Armstrong criteria at the time of PET examination. All patients, including early-stage cases, exhibited asymmetric tracer uptake contralateral to their symptom-dominant side in the cerebral cortex/subcortical white matter and striatum (100%). The sensitivity for detecting asymmetric imaging abnormalities contralateral to the symptom-dominant side was 86.7% for brain MRI, 81.8% for perfusion SPECT, and 90% for DAT SPECT. White matter volume reduction was observed in the subcortical region of the precentral gyrus with increased THK5351 uptake, occurring significantly more frequently than gray matter volume reduction. THK5351 PET may be a sensitive imaging technique for detecting asymmetric CBS pathologies, including those in early stages.

Anti-LGI1 Encephalitis Developing Immunoglobulin Responsive Orthostatic Hypotension after Remission.

Anti-leucine-rich glioma-inactivated 1 (LGI1) antibody is associated with limbic encephalitis. We herein report a patient with anti-LGI1 encephalitis who developed severe orthostatic hypotension (OH) responsive to immunoglobulin therapy five years after developing symptoms of encephalitis. A 71-year-old man presented with amnesia caused by limbic encephalitis. The symptoms of encephalitis improved partially without any immunotherapy. Five years later, he developed severe OH, and anti-LGI1 antibody was positive. The catecholamine dynamics indicated that the central autonomic nervous system was the lesion of his OH. Intravenous immunoglobulin therapy improved the OH. This case suggests that anti-LGI1 antibody can be associated with severe OH.

White matter lesions and cognitive impairment may be related to recovery from unilateral spatial neglect after stroke.

BACKGROUND: Unilateral spatial neglect (USN) is frequently found in ischemic stroke patients. Because USN is related to poor functional outcomes, evaluating recovery from USN after stroke is critical. METHODS: Patients with acute ischemic stroke with lesions in the right cerebral hemisphere on MRI and exhibiting left USN were administered the Behavior Inattention Test (BIT) at 1 and 3weeks after admission. BIT improvement was defined as a ≥1-point increase in ≥4 of the 6 BIT subtests from 1 to 3weeks, or a total BIT score ≥131 at 3weeks. Factors associated with improvement of left USN were analyzed. RESULTS: Eighteen patients (8 men; mean age, 70±12years) were enrolled in this study. BIT was performed at 5.3±0.7 and 18.2±0.7days after admission. Twelve patients were classified to the improvement (I) group, and 6 to the non-improvement (NI) group. BIT scores increased substantially from 76.6±40.5 in the acute phase to 109.2±43.3 in the subacute phase. The I group displayed higher BIT scores than the NI group in both acute and subacute phases (P<0.01 each). The degree of white matter lesions on the Fazekas scale was lower in the I group (0.6±0.7) than in the NI group (1.7±1.2, P=0.028). Increased BIT scores correlated significantly with increased Mini Mental State Examination scores (r=0.487, P=0.040). CONCLUSIONS: Amelioration of left USN might be related to white matter lesions and cognitive impairment. Sample size in the current study was small, limiting the generalizability of results, and larger studies are warranted in the future.

The Neural Basis of Typewriting: A Functional MRI Study.

To investigate the neural substrate of typewriting Japanese words and to detect the difference between the neural substrate of typewriting and handwriting, we conducted a functional magnetic resonance imaging (fMRI) study in 16 healthy volunteers. All subjects were skillful touch typists and performed five tasks: a typing task, a writing task, a reading task, and two control tasks. Three brain regions were activated during both the typing and the writing tasks: the left superior parietal lobule, the left supramarginal gyrus, and the left premotor cortex close to Exner's area. Although typing and writing involved common brain regions, direct comparison between the typing and the writing task revealed greater left posteromedial intraparietal cortex activation in the typing task. In addition, activity in the left premotor cortex was more rostral in the typing task than in the writing task. These findings suggest that, although the brain circuits involved in Japanese typewriting are almost the same as those involved in handwriting, there are brain regions that are specific for typewriting.

Memory impairment following right cerebellar infarction: a case study.

We reported a patient with a right cerebellar infarction who showed anterograde amnesia. Cognitive dysfunction caused by cerebellar lesions was called cerebellar cognitive affective syndrome, and deactivation of the contralateral prefrontal cortex function due to disconnections of cerebello-cerebral fiber tracts have been hypothesized as mechanism underlying the syndrome. The episodic memory impairment, however, could not be supported by the same mechanism because the prefrontal lesions cannot cause amnesia syndrome. The feature of the impairment of our patient was similar to that of diencephalic amnesia, and a single photon emission computed tomography study showed a relative hypoperfusion in the right cerebellar hemisphere and left anterior thalamus. We considered that the memory deficit was caused by the dysfunction of the thalamus, which is a relay center of the cerebello-cerebral connectivity network.

[A 53-year-old man with herpes encephalitis showing acceleration of improvement in higher brain function after general anesthesia with sevoflurane: a case report].

We experienced a right-handed 53-year-old man who presented with disturbance of consciousness and fever. Herpes simplex encephalitis (HSE) was diagnosed based on the detection of herpes simplex virus DNA in the cerebrospinal fluid. The administration of acyclovir for 42 days improved his consciousness level. Drowsiness, fever and seizures reappeared 20 days after stopping acyclovir treatment (day 67) and he responded well to vidarabine and methylprednisolone pulse therapy. An assessment of aphasia on day 98 revealed transcortical sensory aphasia. Brain MRI showed lesion in the left temporal lobe, bilateral insular cortexes and bilateral frontal lobe. His higher brain dysfunction continued. On day 156, he underwent hip replacement arthroplasty under general anesthesia sevoflurane. His higher brain dysfunction rapidly improved thereafter. We concluded that the accelerated improvement in our patient's higher brain function was related to the protective effect of sevoflurane. Some reports also show the protective effects of sevoflurane in experimental allergic encephalomyelitis by inhibition of T cell activation. These protective and anti-inflammatory effects may explain the accelerated improvement in higher brain function after general anesthesia.

Frontotemporal lobar degeneration with writing disturbance mainly consisting of omission of kana letters.

A right-handed woman developed pseudobulbar palsy and a particular writing disturbance mainly composed of omission of kana letters (OKL) at the age of 79, followed by gradual progression of generalized motor disturbance and mutism. She died at the age of 88. Postmortem examination revealed frontotemporal lobar degeneration. The precentral cortex and premotor area were the most severely degenerated among the affected frontal, parietal, and temporal lobes. The omission of kana letters has been recently reported as a characteristic feature of writing disturbance in Japanese amyotrophic lateral sclerosis (ALS). Our case indicates that OKL is not specific to ALS, and that the prefrontal and precentral cortices, common lesions between our case and ALS, are responsible for OKL. This case also shows that OKL can be caused by a pathomechanism independent from other types of writing error. The neurolinguistic analysis of our case suggests the disturbance of the moraic frame of words in the transcription process of morae into kana letters or kana-letter cards.

The role of the thalamus in recovery from tactile extinction and crossed tactile extinction.

A 68-year-old man had a cerebral infarction affecting the right parietal lobe, right insula, and the left prefrontal region. On admission, left hand tactile extinction was noted when the hands were placed both in anatomical and crossed positions, but was noted only in crossed positions from day 20 and later. Five months later, the patient developed another cerebral infarction in the right thalamus, and left hand tactile extinction was again seen both in the anatomical and crossed positions. Our findings suggest that the thalamus was involved in the recovery from the tactile extinction in anatomical positions.

[Neuropsychology of consciousness].

The nature of the relation between neuropsychology and consciousness has become a major issue. DB had a left lower quadrant hemianopia. When questioned about his vision in the left lower field, DB reported that he saw nothing. When DB was asked to point to locations in the impaired field in which spots of light were turned on briefly, he was surprisingly accurate. Apparently, even though DB could not consciously perceive a light in his blind region, his brain knew where it had appeared. This phenomenon has become known as blindsight. DF suffered carbon monoxide poisoning. The result in DF was an extensive lesion of the lateral occipital region, including cortical tissue in the ventral visual pathway. The principal deficit that DF experienced was a severe inability to recognize objects, which is known as visual form agnosia. Despite her inability to identify objects or to estimate their size and orientation, DF still retained the capacity to appropriately shape her hand when reaching out to grasp something. The anoxic episode affected her vision for perception, but left her vision for action largely unscathed. These patients lack conscious awareness about some subset of information, even though he or she processes that information unconsciously.

Ambient echolalia in a patient with germinoma around the bilateral ventriculus lateralis: a case report.

Ambient echolalia is a rare condition with few reported cases. We report the case of a 20-year-old man with a germinoma around the bilateral ventriculus lateralis who exhibited ambient echolalia. Clinical features included instinctive grasp reaction and compulsive manipulation of tools in his right hand. Speech or mental deterioration has been cited as a cause of ambient echolalia, but neither dementia nor aphasia was present. We propose that ambient echolalia in our case could be interpreted as a disinhibition of pre-existing essentially intact motor subroutines due to damage of the medial frontal lobe.

[The symptomatology of frontal and temporal lobe damages].

In this paper, we review the symptoms associated with damages to the frontal and/or temporal lobes. Similarities and differences between the symptoms observed after a stroke and in frontotemporal lobar degeneration are also discussed. Frontal lobe damages may lead to various apraxic disorders, including limb-kinetic, ideomotor, gait, buccofacial, and ocular motor apraxia. Language dysfunction can arise from perisylvian lesions as well as from extra-perisylvian regions. Broca's aphasia, Wernicke's aphasia, pure word deafness, and aphemia are typical examples of disorders caused by damages to the perisylvian region. Transcortical motor and anomic aphasias are mostly associated with damages to the extra-perisylvian region. Although it has been reported that executive dysfunction is associated with damages to the frontal lobe, it remains to be determined whether there is a cause-and-effect relationship between the 2. A combination of memory, attention, emotional, and mood disorders may underlie executive dysfunction. Patients with lesions in the inferior temporal lobe often present with various types of agnosia. Visual agnosia is common in semantic dementia, but is infrequent after a stroke in the temporal lobe. Prosopagnosia is a rare consequence of damages to the temporal lobe. Bilateral and right-sided lesions are likely to cause this disorder than left-sided lesions. Although, prosopagnosia is less frequently observed than visual agnosia in semantic dementia, it still is one of the common features of the disease. Bilateral injuries to the mesial temporal lobes have been known to induce a marked amnesic syndrome. It is devastating in that the patient can remember virtually nothing new. However, memories acquired before the injuries are mostly conserved and the patient can still learn motor skills.

Right-sided neglect influences the writing of Kanji: A case study.

Neglect is the failure to report, respond, or orient to novel or meaningful stimuli presented to the side opposite a brain lesion. Here we describe the case of a 73-year-old woman who experienced a writing deficit in the right-sided component of Kanji letters (morphograms) of the Japanese language. Magnetic resonance imaging of the brain showed an infarction in the left middle temporal and occipital gyrus. The patient wrote recognizable, well-formed but paragraphic Kanji letters in both spontaneous and dictated writing. Most letters are composed of two elements: "hen" (left) and "tsukuri" (right). Neographism in tsukuri was her most frequent error. When she was instructed to answer orally hen and tsukuri, she made more mistakes related to tsukuri than to hen. Unilateral spatial neglect in memory or imagery was reported. We concluded that unilaterally disrupted processing of internal representations affected the writing of Kanji letters in this patient.

Hyperlexia and ambient echolalia in a case of cerebral infarction of the left anterior cingulate cortex and corpus callosum.

We report the case of a 69-year-old woman with cerebral infarction in the left anterior cingulate cortex and corpus callosum. She showed hyperlexia, which was a distinctive reading phenomenon, as well as ambient echolalia. Clinical features also included complex disorders such as visual groping, compulsive manipulation of tools, and callosal disconnection syndrome. She read words written on the cover of a book and repeated words emanating from unrelated conversations around her or from hospital announcements. The combination of these two features due to a focal lesion has never been reported previously. The supplementary motor area may control the execution of established subroutines according to external and internal inputs. Hyperlexia as well as the compulsive manipulation of tools could be interpreted as faulty inhibition of preexisting essentially intact motor subroutines by damage to the anterior cingulate cortex reciprocally interconnected with the supplementary motor area.

Agraphia in intellectually normal Japanese patients with ALS: omission of kana letters.

To investigate the occurrence of a writing defect, omission of kana letters (OKL), in intellectually normal Japanese patients with amyotrophic lateral sclerosis (ALS), and define the neuroimaging profile of OKL. Sixteen Japanese adults (10 men and 6 women), similar in age (mean 62.9 +/- 9.9 years) and level of education (mean 12.6 +/- 2.13 years), with early-stage, classical ALS (mean duration 15.9 +/- 5.45 months) were investigated, including tests of motor function and ALS progression; intellectual function including writing ability; and neuroimaging, with follow-up of 1 year. Main outcome measures were as follows: Raven's Colored Progressive Matrices (RCPM: intellect and psychomotor speed); one-minute verbal fluency measurement; paired associate word-learning test (PAWLT); Western Aphasia Battery (WAB); moraic segmentation test; magnetic resonance imaging (MRI); and (123)I-isopropyl amphetamine ((123)I-IMP) or (99m)Tc-ethylcysteinate dimmer (ECD) single photon emission tomography (SPECT). Three patients (18.8%) showed OKL (WAB), with disturbance in moraic segmentation. One patient showed decreased blood flow to the bilateral frontal lobes by (123)I-IMP-SPECT. Patients with OKL did not differ significantly from those without in the RCPM (intellect), RCPM (time), verbal fluency, or PAWLT (p = 0.10, 0.84, 0.63, 0.55). Although motor dysfunction and weakness progressed during follow-up, none developed symptoms of dementia. The OKL may develop as a relatively early cognitive symptom in intellectually normal Japanese patients with classical ALS. The neuroimaging profile of OKL remains uncertain.

[Alien hand sign observed at the initial stage of a case of Creutzfeldt-Jakob disease].

A 68-year-old man was admitted to our hospital in the mid-October of 2006 because of a one-month history of peculiar movements of the left hand, which had been preceded by one month by awkward motions in the left leg. Upon neurological examination, spontaneous involuntary movement of the left hand was found. His left hand with his index finger stretched moved toward his right side spontaneously. He could not control his left leg freely. Although he showed mild ataxia in his left hand, there was no weakness, no dystonia, and no apraxia. No sensory abnormality was detected except for mild deep-sensation impairment in his left foot. The results of magnetic resonance imaging (MRI) including diffusion-weighted imaging (DWI) were normal; however, single-photon emission computed tomography (SPECT) showed hypoperfusion in the right hemisphere. At the time of admission, although a clinical diagnosis could not be made, we considered that the involuntary movements of his left hand were consistent with alien hand sign (AHS). Two and a half months after its onset, with the development of rapidly progressive dementia and generalized myoclonus, AHS gradually disappeared. Three months after the AHS onset, MRI with DWI showed restricted diffusion within the cortex involving the cingulated gyrus and bilateral temporal lobes, which was more prominent on the right than on the left side. Four months after the AHS onset, 14-3-3 protein level of the cerebrospinal fluid was elevated, and EEG recordings showed diffuse slowing of basic activity with periodic complexes. The patient was clinically diagnosed as having CJD. The patient died of pneumonia four and a half months after the AHS onset. AHS has rarely been reported in patients with CJD. Our case illustrates the importance of considering CJD in the differential diagnosis, if the patient showed AHS, even with normal MRI findings.

Anti-Ma2 paraneoplastic encephalitis associated with testicular germ cell tumor treated by carboplatin, etoposide and bleomycin.

Anti-Ma2-associated encephalitis is a paraneoplastic disorder that predominantly affects the limbic system, diencephalon and brainstem, and is usually associated with tumors of the testis. We report a 35-year-old man with a right testicular mass who presented with multiple neurological complains, and clinical, serological and radiological features compatible with anti-Ma2-associated encephalitis. After three courses of carboplatin, etoposide and bleomycin for metastatic testicular germ-cell tumor, all elevated tumor markers normalized and the retroperitoneal metastases disappeared, but the neurological disorder deteriorated. To our knowledge, this is the first case in which orchiectomy followed by carboplatin, etoposide and bleomycin for a testicular tumor with anti-Ma2 encephalitis was performed.

A case of auditory agnosia with impairment of perception and expression of music: cognitive processing of tonality.

There is fairly general agreement that the melody and the rhythm are the independent components of the perception of music. In the theory of music, the melody and harmony determine to which tonality the music belongs. It remains an unsettled question whether the tonality is also an independent component of the perception of music, or a by-product of the melody and harmony. We describe a patient with auditory agnosia and expressive amusia that developed after a bilateral infarction of the temporal lobes. We carried out a detailed examination of musical ability in the patient and in control subjects. Comparing with a control population, we identified the following impairments in music perception: (a) discrimination of familiar melodies; (b) discrimination of unfamiliar phrases, and (c) discrimination of isolated chords. His performance in pitch discrimination and tonality were within normal limits. Although intrasubject statistical analysis revealed significant difference only between tonality task and unfamiliar phrase performance, comparison with control subjects suggested a dissociation between a preserved tonality analysis and impairment of perception of melody and chords. By comparing the results of our patient with those in the literature, we may say that there is a double dissociation between the tonality and the other components. Thus, it seems reasonable to suppose that tonality is an independent component of music perception. Based on our present and previous studies, we proposed the revised version of the cognitive model of musical processing in the brain.