Case 32 – Left or Right: Which Way to Go?

Abstract

A 73-year-old Brazilian, right-handed man, retired business manager, began having progressively cognitive and behavioral disorders for the past 5 years. His family noticed some behavioral changes, as he presented with great irritability, usage of bad language, profound inhibition, apathy, and unprecedented religious interests (hyper-religiosity). He had no history of hallucinations. During the consultation, the patient recurrently said in a delirious speech that he was a “disgrace,” that he was disturbing his wife and family, and it would be a relief if he died. His conversation was predominantly melancholic and mostly about self-centered themes.

Case 32 Left or Right: Which Way to Go?

André Aguiar Souza Furtado de Toledo , Karoline Carvalho Carmona , Leonardo Cruz de Souza , and Paulo Caramelli

32.1 Case History

He also had difficulties with his memory. According to him, his “memory did not exist.” He insidiously started to have problems in episodic memory. He noted he was having difficulty in retaining information from newspapers and TV shows, but still could remember numerical information and important meetings. He also started to have language problems, such as incapacity in understanding written material or comprehending complex speeches (e.g., concatenated ideas). Apparently his autonomy for daily life activities, like financial tasks and driving, remained preserved, although he decided to leave his job due to his cognitive problems. He had no history of traumatic brain injury, seizures, stroke, or alcoholism. He has a history of rheumatoid arthritis and current medications included nonsteroidal anti-inflammatory drugs and methotrexate. There was no family history of dementia.

On examination, the patient was alert and fully oriented. Cranial nerves were intact. On motor exam, his tone and power were normal, although he had increased reflexes globally. Gait, coordination, and sensory examination were normal, and there were no signs of parkinsonism. On cognitive testing, his performance in the Mini-Mental State Examination (MMSE) was 27/30 as he missed the three words on delayed recall. He did quite well in the Brief Cognitive Battery (BCB), presenting some difficulty naming simple figures such as key and turtle.¹ The clock-drawing test was normal. When asked to write irregular words, the patient miswrote less than a half of them (clinical profile compatible with surface dysgraphia). The physical examination was otherwise normal.

Screening laboratory tests for reversible causes of dementia were ordered and all results were within normal ranges, including blood count, comprehensive metabolic panel, thyroid-stimulating hormone, vitamin B12, and venereal disease research laboratory. A magnetic resonance imaging (MRI) was performed and revealed moderate atrophy of the right anterior temporal lobe. A new MRI (2 years later) demonstrated increase of the right anterior temporal atrophy and also atrophy involving the anterior parts of the left temporal lobe, although less severe (Figures 32.1 and 32.2). Single-photon emission computed tomography (SPECT) displayed focal hypoperfusion of the right temporal lobe.

Figure 32.1 MRI (FLAIR sequence; axial slices) showing the temporal lobes at the level of the optic nerves. Note the atrophy of the anterior temporal lobes, most prominently in the right side (upper left side of the images).

Figure 32.2 MRI (T2 sequence; coronal slices). Note the atrophy of the anterior temporal lobes, most prominently in the right side (lower left side of the images).

Based on the overall clinical, neuropsychological, and neuroimaging data a probable diagnosis of frontotemporal dementia (right temporal variant) was made.

32.2 Discussion

Frontotemporal dementia (FTD) constitutes a group of neurodegenerative diseases that are clinically, pathologically, and genetically heterogeneous. It is known as a predominant early-onset dementia and is considered one of the most common causes of dementia in adults younger than 60 years of age, with the onset of symptoms typically occurring in the sixth decade of life. While the expression FTD refers to the clinical syndrome, frontotemporal lobar degeneration (FTLD) is related to the anatomical concept of selective neuronal degeneration in frontal and temporal lobes that is observed in most of the patients with FTD.²^, ³

The three major clinical presentations include the frontal or behavioral variant (bvFTD), the temporal variant (tvFTD; also known as semantic dementia, SD), and the progressive nonfluent aphasia (PNFA; also known as primary progressive aphasia nonfluent/agrammatic type, nfPPA).⁴ These clinical syndromes differ from each other by different atrophy patterns, which explain the degrees of personality change, executive dysfunction, and language impairment.

Patients diagnosed with bvFTD usually exhibit exuberant behavioral changes, like disinhibition, apathy, loss of empathy, ritualistic or stereotyped behaviors, hyperorality and changes in eating preferences. Moreover, these patients may show deficits in social cognition and executive functions. Neuroimaging studies typically indicates atrophy predominantly frontal-insular rather than temporal.² The bvFTD is by itself a heterogeneous disorder. A study conducted by Whitwell and colleagues with sixty-six subjects with clinical diagnosis of bvFTD showed that patients within this clinical syndrome could be divided into four different subtypes on an anatomical basis – two of which are defined by important frontal atrophy and the other two by predominant temporal lobe atrophy. Moreover, the temporal prominent subtype showed different patterns of gray matter loss, since one was restricted to the inferior and medial lobes, especially in the right temporal lobe, named “temporal-dominant” subtype. Patients with this subtype performed worse on tests of naming and memory than the other three subtypes, as well as showed a high proportion of changes in appetite and eating behavior, without apathy as a common feature. These results confirmed that a right dominant temporal atrophy can occur in the context of bvFTD and not just in semantic dementia.⁵

Whereas in bvFTD, asymmetrical distribution of atrophy across the hemispheres is less frequent, in SD there is significant lateralization of atrophy, with the distribution of degeneration across hemispheres being highly asymmetrical, primarily in the early stages of the disease. Moreover, SD is associated with asymmetrical atrophy of the anterior temporal lobes, frequently greater on the left. Classic descriptions of SD used to emphasize the cognitive features of the disease, but recent studies found that behavioral symptoms are also common in this variant, simulating changes typically found in bvFTD.

In this context, a (new) variant has been described by an increasing number of case reports presenting patients with either progressive loss of self-identification and knowledge or prominent changes in behavior. However, there are still fewer case reports describing this clinical-genetic-pathological entity, named here as right temporal variant frontotemporal dementia (RtvFTD). The literature usually addresses the RtvFTD by three main perceptions: (1) an atypical form of bvFTD, as it exhibits an asymmetrical right temporal lobe atrophy (the temporal-dominant subtype described previously); (2) a subtype of the SD syndrome with a major involvement of the right temporal lobe and with more exuberant behavioral manifestation; and (3) a new anatomical variant of FTD, with some sort of clinical-pathological homogeneity.⁶ As can be seen, the shortage of knowledge about RtvFTD makes it a still undefined entity, a disorder within a clinical-genetic-pathological gradient between bvFTD and SD (Figure 32.3).