A case of frontotemporal dementia 1

Heng Siang Ting1, B M Yashodhara2, Uduman Ali Mohamed Yousuf3, Bashir Ahmad Dar2,
Adinegara Lutfi Abas4 1Final year Medical Student, Melaka Manipal Medical College, Melaka,
Malaysia. 2Associate Professor, Department of Medicine, Melaka Manipal Medical College,
Melaka, Malaysia.
3HOD, Department of Medicine, Melaka Manipal Medical College, Melaka, Malaysia.
4Deputy Dean, HOD, Department of Community Medicine, Melaka Manipal Medical College,
Melaka, Malaysia.
Abstract

Introduction:

Frontotemporal dementia is a common cause of dementia. It is easily misdiagnosed as a

psychiatric illness due to its presentation with behavioral problems, mutism, language problems
and in some cases with aggression and anti-social behavior.

Case Report: We report a case of a 72-year-old man who presented with behavioral
abnormalities, lack of personal hygiene, personality changes of gradual onset since 2–3 years,
suggested by inability to take care of self, mutism, social disinhibition in the form of micturition
in the presence of family members. Computed tomography (CT) scan of the brain showed
atrophy of frontal and temporal lobes. The family members were counseled for the outcome
and prognosis of the case.

Conclusion: The diagnosis of frontotemporal dementia is made based on presentation,

diagnostic criteria and brain imaging. Definite treatment is not available, but treating according
to presenting complaints of the patient is helpful; e.g. if the patient has depression, anti-
depressants along with family counselling about the progression of the disease and awareness
about requirement for the family support are important.

Keywords: Dementia, Frontotemporal, Abnormal behavior, Poor personal hygiene

Introduction

Dementia is a common disease in middle age and elderly. It may be due to Alzheimer's disease,
vascular dementia, frontotemporal dementia (FTD) or Lewy body dementia. It may also be due
to secondary causes like HIV infection, Huntington's disease, head injury, Parkinson's disease,
metabolic and endocrine diseases, poisoning, infections like neurosyphilis, vitamin
deficiencies, normal pressure hydrocephalus and pseudo-dementia due to depression.

Alzheimer disease patients typically present with problems in cognitive functions; memory,
executive functions, language and constructional praxis. On brain scanning there is atrophy of
the brain from occipital lobe to parietal lobe and later in the disease of the frontotemporal
areas. Patients tend to get lost and find it difficult to get back to their place due to problems in
visual-spatial skills. They also lose things easily. Patients of frontotemporal dementia typically
have problems in behavior, personality and language when assessed by neuropsychiatric
battery of tests but have intact visual-spatial skills. The presenting features are in the form of
behavioral abnormalities like anti-social conduct, poor personal grooming, thefts and vehicle
accidents. Generally the diagnosis is not made early by non-specialists, even though it is one of
the common causes of dementia.
Case Report
2
A 72-year-old man presented with history of poor oral intake for two days,
chills and rigors, without the presence of fever on daily temperature REPORTE DE
recording. As he was not able to give accurate history, his daughter was
interviewed and it was found that the patient has had personality change for
CASO
2–3 years now. It was insidious in onset and progressively worsening.
72 AÑOS
Daughter noticed that patient had problems with memory, particularly short
term memory loss, with patient not being able to remember the task he was historial de ingesta
doing at a time. Patient was also found to have multiple, minor, motor vehicle oral deficiente
accidents, but he was not able to recall what happened. Patient also durante dos días,
frequently misplaced things. The patient could still recognize family escalofríos y
cansancio, sin la
members, and was able to drive out alone without getting lost. For the past
presencia de fiebre
one year, patient had a gradual onset of disinhibition. He did not have urinary
incontinence, but he would urinate anywhere and anytime at home even in cambios de
the presence of other family members. He also became more reserved, personalidad durante
communicated poorly with family members and at times was found to be dos o tres años
non-responsive to questions. Patient's daughter also noticed that patient has inicio insidioso
peculiar behaviors on and off; such as sudden thought block and smiling to
pérdida de memoria a
himself. He did not have visual hallucinations. The daughter also noticed the
corto plazo
patient having a vesicular skin lesion on left thigh which was painful and not
itchy. There was no history of previous head trauma, no fever, no movement múltiples accidentes
menores de vehículos
disorders and no history of frank delusion or hallucination. There was no
de motor
previous history of psychiatric disorder in the patient or family members. On
examination, the patient was alert and conscious with GCS (GLASGOW COMA extravía cosas con
frecuencia
SCALE)15/15. However, he was not paying attention to his surroundings. He
was afebrile, pulse rate was 83 beats per min, and blood pressure was aún podía reconocer a
128/62 mmHg. A tender, erythematous vesicular lesion was found on left los miembros de la
familia
thigh. All cranial nerves were found to be intact. Speech was normal, but at
times patient would become mute. His mini mental state examination podía conducir solo sin
(MMSE) score was 21/30, as assessed recently on follow up by one of the perderse
attending neurologist. He was found to have positive sucking, palmo-mental *inicio gradual de
reflexes. Rest of central nervous system examination and other examinations desinhibición
for respiratory, cardiovascular, gastrointestinal and musculoskeletal systems
*No tenía incontinencia
were essentially normal. urinaria, pero orinaría
en cualquier lugar y en
Un hombre de 72 años presentó un historial de ingesta oral deficiente cualquier momento en
durante dos días, escalofríos y cansancio, sin la presencia de fiebre en el casa, incluso en
registro de la temperatura diaria. Como no pudo dar una historia exacta, se presencia de otros
entrevistó a su hija y se descubrió que el paciente ha tenido cambios de miembros de la familia
personalidad durante dos o tres años. Fue insidioso en el comienzo y bloqueo de
empeoró progresivamente. La hija notó que el paciente tenía problemas con pensamiento repentino
la memoria, particularmente pérdida de memoria a corto plazo, y el paciente y sonriendo a sí mismo
no podía recordar la tarea que estaba haciendo a la vez. También se encontró
que el paciente tenía múltiples accidentes menores de vehículos de motor,
pero no pudo recordar lo que sucedió. El paciente también extravía cosas con
frecuencia. El paciente aún podía reconocer a los miembros de la familia y
podía conducir solo sin perderse. Durante el último año, el paciente tuvo un
inicio gradual de desinhibición. No tenía incontinencia urinaria, pero orinaría
en cualquier lugar y en cualquier momento en casa, incluso en presencia de otros miembros de
3
la familia. También se volvió más reservado, se comunicó mal con los miembros de la familia y,
a veces, no respondía a las preguntas. La hija del paciente también notó que el paciente tiene
comportamientos peculiares intermitentes; como bloqueo de pensamiento repentino y
sonriendo a sí mismo. Él no tenía alucinaciones visuales. La hija también notó que el paciente
tenía una lesión vesicular en la piel del muslo izquierdo que era dolorosa y no picaba. No hubo
antecedentes de traumatismo craneoencefálico previo, ni fiebre, ni trastornos del movimiento,
ni antecedentes de delirios o alucinaciones. No hubo antecedentes de trastorno psiquiátrico en
el paciente o miembros de la familia. En el examen, el paciente estaba alerta y consciente con
GCS(GLASGOW COMA SCALE) 15/15. Sin embargo, él no estaba prestando atención a su
entorno. Estaba afebril, la frecuencia del pulso era de 83 latidos por minuto y la presión arterial
era de 128/62 mmHg. Se encontró una lesión vesicular eritematosa y dolorosa en el muslo
izquierdo. Todos los nervios craneales se encontraron intactos. El habla era normal, pero a veces
el paciente se volvía mudo. Su puntaje de mini examen del estado mental (MMSE) fue 21/30,
según lo evaluado recientemente en el seguimiento por uno de los neurólogos asistentes. Se
descubrió que tenía un reflejo de succión positiva, reflejos palmo-mentales. El resto del
examen del sistema nervioso central y otros exámenes para los sistemas respiratorio,
cardiovascular, gastrointestinal y musculoesquelético fueron esencialmente normales

Patient's full blood count, renal functions, thyroid functions, liver functions and routine urine
examinations were normal. He tested negative for HIV, Hepatitis B, Hepatitis C, venereal
disease research laboratory test (VDRL), and treponema palladium hemagglutination test
(TPHA). His serum electrolytes were normal. Based on the history and clinical presentation, a
diagnosis of dementia with Herpes simplex of left thigh was considered. Computed
tomography scan of the brain showed atrophy of frontal and temporal areas of the brain.
(Figure 1) (Figure 2) (Figure 3) (Figure 4)

El conteo sanguíneo completo del paciente, las funciones renales, las funciones tiroideas, las
funciones hepáticas y los exámenes de orina de rutina fueron normales. Dio negativo para el
VIH, Hepatitis B, Hepatitis C, prueba de laboratorio de investigación de enfermedades venéreas
(VDRL) y prueba de hemaglutinación con treponema paladio (TPHA). Sus electrolitos séricos eran
normales. Con base en la historia y la presentación clínica, se consideró un diagnóstico de
demencia con herpes simple del muslo izquierdo. La tomografía computarizada del cerebro
mostró atrofia de las áreas frontales y temporales del cerebro.

A find diagnosis of frontotemporal dementia with rash due to herpes simplex infection on left
thigh was made. He received acyclovir 200 mg 5 times a day for 5 days at discharge. The daughter
was counseled about the disease and its progression and follow up. The family members were
very supportive to the patient. They were advised to not to let patient drive on his own.

Se realizó un diagnóstico de hallazgo de demencia frontotemporal con erupción debido a una

infección por herpes simple en el muslo izquierdo. Recibió acyclovir 200 mg 5 veces al día
durante 5 días al momento del alta. La hija fue aconsejada sobre la enfermedad y su progresión
y seguimiento. Los miembros de la familia fueron muy solidarios con el paciente. Se les aconsejó
que no dejaran que el paciente manejara solo.
 4

Figure 1: Bifrontotemporal atrophy and prominent sylvian fissures. Frontal horns of

ventricles are just visible.

Figure 2: Bifrontotemporal atrophy and prominent sylvian fissures. Frontal horns of ventricles
are clearly visible.

Discussion

Frontotemporal dementia is one of the causes of early-onset dementia (EOD) and has a 2.6%
prevalence. Vascular dementia (42.5%), and Alzheimert disease (25.6%) are the most common
causes, as noted in a population based study from Japan. [1] Frontotemporal dementia is a focal
form of dementia in the presenium, yet remains poorly recognized, [2] It is frequently mistaken
for Alzheimer's disease or psychiatric diseases. [3] The age of onset of FTD is somewhat younger
than other degenerative dementias, with a mean age of onset of about 58 years. [4] [5] It is now
recognized as one of the three types of frontotemporal lobar degenerations (FTLD);
frontotemporal dementia, semantic dementia and progressive nonfluent aphasia [PNFA]. [5]
The prevalence of FTD is variable in different age ranges: 3.6/100000 at age 50–59 years,
9.4/100000 at age 60–69 years and 3.8/100000 at age 70–79 years. [4] The reported age of onset
ranges from 33 to 80 years, [4] with a male predominance in FTD and semantic dementia: [5]
Frontotemporal dementia is the second most common cause of dementia in patients less than
65 years of age. [5] Our patient developed frontotemporal dementia of 72 years of age.
La demencia frontotemporal es una de las causas de la demencia de
5
inicio temprano (EOD) y tiene una prevalencia del 2,6%. La demencia
vascular (42.5%) y la enfermedad de Alzheimer (25.6%) son las causas
más comunes, como se observó en un estudio poblacional de Japón. UBIQUITINA
[1] La demencia frontotemporal es una forma focal de demencia en el
La ubiquitina (o ubicuitina) es
presenio, aunque sigue siendo poco reconocida, [2] con frecuencia se
una pequeña proteína
confunde con la enfermedad de Alzheimer o las enfermedades reguladora que ha sido
psiquiátricas. [3] La edad de inicio de FTD es algo más joven que otras encontrada en la mayoría de
demencias degenerativas, con una edad media de inicio de alrededor los tejidos de los organismos
de 58 años. [4] [5] Ahora se reconoce como uno de los tres tipos de eucariotas. Una de sus muchas
funciones es dirigir el reciclaje
degeneraciones lobulares frontotemporales (FTLD); demencia de proteínas. La ubiquitina
frontotemporal, demencia semántica y afasia progresiva no fluida puede asociarse a proteínas y
[PNFA]. [5] La prevalencia de FTD es variable en diferentes rangos de marcarlas para su destrucción.
edad: 3.6 / 100000 a la edad de 50-59 años, 9.4 / 100000 a la edad de El marcaje de ubiquitina dirige
las proteínas al proteosoma,
60-69 años y 3.8 / 100000 a la edad de 70-79 años. [4] La edad de inicio
que es un gran complejo de
informada oscila entre 33 y 80 años, [4] con predominio masculino en proteínas que encontramos en
FTD y demencia semántica: [5] La demencia frontotemporal es la la célula y que degrada y
segunda causa más común de demencia en pacientes menores de 65 recicla proteínas innecesarias.
años. [5] Nuestro paciente desarrolló demencia frontotemporal de 72 Este descubrimiento ganó el
premio Nobel en química en
años de 2004.12
Macroscopic examination of the brain of a patient with FTLD typically
shows symmetrical focal atrophy of the frontal lobes, temporal lobes. Microscopic examination
of the cerebral cortex in most forms of FTLD, shows microvacuolation and neuronal loss. On
staining for deposits in neurons, abnormal tau protein aggregates (46%) and ubiquitin-positive
inclusions (29%) were found.[6] Our patient had frontal and temporal lobe atrophy on CT scan.
The exact etiology and pathophysiology of frontotemporal dementia is incompletely understood
but recent studies suggest that genetics plays an important role in disease causation. [7] This is
supported by the fact that about 50% of patients with frontotemporal dementia (FTD) report a
positive family history. [7]

El examen macroscópico del cerebro de un paciente con FTLD típicamente muestra una atrofia
focal simétrica de los lóbulos frontales, los lóbulos temporales. El examen microscópico de la
corteza cerebral en la mayoría de las formas de FTLD, muestra microvacuolación y pérdida
neuronal. Al teñir los depósitos en las neuronas, se encontraron agregados de proteína tau
anormales (46%) e inclusiones ubiquitin positivas (29%). [6] Nuestro paciente tenía atrofia del
lóbulo frontal y temporal en la tomografía computarizada. La etiología y fisiopatología exactas
de la demencia frontotemporal no se conocen por completo, pero estudios recientes sugieren
que la genética juega un papel importante en la causalidad de la enfermedad. [7] Esto es
respaldado por el hecho de que aproximadamente el 50% de los pacientes con demencia
frontotemporal (FTD) informan un historial familiar positivo. [7]

Patients with FTD display a heterogeneous clinical picture, which may include behavioral,
cognitive, and motor manifestations. [8] They can be divided into two variants: the behavioral
variant and the language variant (also referred as primary progressive aphasia). [8] The
behavioral variant, which was a likely variant in our patient is characterized by progressive
personality changes, lack of insight, loss of social awareness, emotional blunting and loss of
empathy. [8] The language variant on the other hand can be further divided into a well-defined
clinic-pathological entity, semantic dementia (SD), and progressive nonfluent aphasia (PNFA).
[8] Progressive nonfluent aphasia is characterized by a progressive deficit in language, starting
6
from anomia and agramatism progressing to dysfluent spontaneous speech and eventually
mutism. [8] Our patient had shown features of mutism, during his admission in the in-patient
department and was also noted by the daughter of the patient. The vesicular rash on the thigh
in our patient, was diagnosed to be due to Herpes simplex and was treated appropriately.

Frontotemporal dementia is largely made by clinical assessment, as in our case. Neuroimaging

studies are equally important to provide supportive evidence for diagnosis as well as to
exclude other structural diseases. [8] Multiple diagnostic criteria to aid in diagnosis (Table 1)
have been devised and published. [9] Treatment mode available for frontotemporal dementia
is very limited as there are no currently FDA-approved diseases modifying treatments. [10]
Hence, off-label medication usage is frequent in the hope to cope with its devastating
functional disability. Antidepressant and antipsychotic medications, (US FDA-approved
treatments for Alzheimer's disease) including cholinesterase inhibitors and memantine have
been used. [10] Antidepressant and antipsychotic medications, [11] have proven to give some
benefits while cholinesterase inhibitors have limited efficacy. [12] The role of memantine in
frontotemporal dementia is under further evaluation studies. [10]

Los pacientes con FTD muestran un cuadro clínico heterogéneo, que puede incluir
manifestaciones conductuales, cognitivas y motoras. [8] Se pueden dividir en dos variantes: la
variante del comportamiento y la variante del lenguaje (también conocida como afasia
primaria progresiva). [8] La variante del comportamiento, que era una variante probable en
nuestro paciente, se caracteriza por cambios progresivos en la personalidad, falta de
perspicacia, pérdida de conciencia social, embotamiento emocional y pérdida de empatía. [8]
La variante del lenguaje, por otro lado, se puede dividir en una entidad clínico-patológica bien
definida, demencia semántica (SD) y afasia progresiva no fluida (PNFA). [8] La afasia progresiva
no fluida se caracteriza por un déficit progresivo en el lenguaje, que comienza desde la anomia
y el agramatismo hasta el habla espontánea y finalmente el mutismo. [8] Nuestro paciente
había mostrado características de mutismo, durante su ingreso en el departamento de
pacientes internos y también fue notado por la hija del paciente. La erupción vesicular en el
muslo en nuestro paciente, se diagnosticó como debida al Herpes simple y se trató
adecuadamente

Conclusion

Frontotemporal dementia is easy to diagnose and should be suspected in middle age and elderly
persons presenting with gradual onset of personality changes, aggressive behavior, apathy and
mutism. It is easily diagnosed by standard criteria and brain scan findings. Family history may be
7
positive in some cases.

La demencia frontotemporal es fácil de diagnosticar y debe sospecharse en personas de

mediana edad y personas mayores que presentan un inicio gradual de cambios de personalidad,
comportamiento agresivo, apatía y mutismo. Se diagnostica fácilmente según los criterios
estándar y los hallazgos del escáner cerebral. Los antecedentes familiares pueden ser positivos
en algunos casos.

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