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CASE REPORT Table of Contents  
Ahead of print publication
A rare case of frontotemporal dementia with amyotrophic lateral sclerosis


1 Junior Resident, Department of Psychiatry, Yenepoya Medical College, Mangalore, Karnataka, India
2 Assistant Professor, Department of Psychiatry, Yenepoya Medical College, Mangalore, Karnataka, India
3 Professor and Head, Department of Psychiatry, Yenepoya Medical College, Mangalore, Karnataka, India

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Date of Submission01-Mar-2021
Date of Acceptance11-Apr-2021
Date of Web Publication31-Aug-2021
 

  Abstract 


Frontotemporal dementia (FTD) is a neurodegenerative disorder characterized by progressive degeneration of the frontal and temporal lobes which typically presents with cognitive symptoms. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive degeneration of upper and lower motor neurons, leading to symptoms of motor weakness. We present a case of behavioral variant of FTD with ALS. The patient presented with changes in his behavior followed by impaired memory and progressive weakness of bilateral upper limbs. Patient eventually developed difficulty swallowing and recognizing faces too. The case highlights the association between FTD and ALS.

Keywords: Amyotrophic lateral sclerosis, frontotemporal dementia, tauopathies, TDP-43 proteinopathies


How to cite this URL:
Bhat M, Kini G, Amithabh S, Kakunje A. A rare case of frontotemporal dementia with amyotrophic lateral sclerosis. Arch Ment Health [Epub ahead of print] [cited 2021 Dec 7]. Available from: https://www.amhonline.org/preprintarticle.asp?id=325047





  Introduction Top


Frontotemporal dementia (FTD) is an umbrella term used to represent three distinct yet closely related syndromes of neurodegenerative disorders, i.e., behavioral variant FTD (bvFTD) and two forms of primary progressive aphasia (PPA), the nonfluent and semantic variants.[1]

Discovery of the C9orf72 gene mutation a decade ago transformed the conventional knowledge that amyotrophic lateral sclerosis (ALS) is purely a motor neuron disease.[2] It was noted that this mutation can cause FTD and ALS together. Since then, the clinical spectrum of FTD has expanded. Currently, several other motor syndromes such as Corticobasal Syndrome (CBS) and progressive supranuclear palsy (PSP) are also recognized to be manifestations of frontotemporal lobar degeneration.[3],[4] We present one such case which gives more evidence for the fact that FTD is clinically a heterogeneous disorder.


  Case Report Top


Mr S, 39-year-old male, was going through financial problems and legal issues 3 years ago when he isolated himself for several months. When he came back home, the patient was noticed to have drastic reduction in his interaction and appeared withdrawn. The patient would get easily irritable, hit his wife and children for no reason, and laugh inappropriately. The patient started making many mistakes in his job. He would listen to recorded conversations over phone repeatedly, would repeat same sentences again and again, collect waste items thrown by others and snatch food items from children, and start eating them.

Since the last 1 year, he would forget that he has had food and would ask for food repeatedly. The patient would forget to take bath and brush his teeth. He would forget to rinse his mouth after brushing and clean himself after going to the toilet and instructions needed to be repeated to him. The patient would forget that his wife is inside the house and would lock the door when he steps outside of his home leaving her locked inside. He also developed difficulty in recognizing faces. In addition, the patient also developed disturbed sleep at night and was seen digging in the graveyard at night.

Furthermore since the last 1 year, the patient gradually developed weakness of both upper limbs. The patient had difficulty in holding spoon, buttoning his shirt. Subsequently, he developed weakness in the lower limbs and had difficulty walking. The patient eventually developed difficulty in swallowing and frequently aspirated his food. The patient lost significant amount of weight. The speech output reduced as he had difficulty talking.

There was no significant past history or family history of psychiatric illness or neurologic illness. Premorbidly, the patient was well adjusted.

On mental status examination, reduced psychomotor activity and speech was noted. The patient had flat affect and insight was poor. On systemic examination, the patient had atrophy of bilateral upper limb and lower limb muscles, hypertonia in bilateral upper and lower limbs, reduced power in all four limbs with visible fasciculation, and spasticity was noted. Exaggerated deep tendon reflexes in bilateral upper and lower limbs and fasciculation in tongue was present. Sensory system examination was normal. Detailed lobe functions could not be assessed due to poor physical condition of the patient.

The patient was diagnosed to have bvFTD with ALS. The patient was admitted and treated with Riluzole 50 mg BD and was given Quetiapine 100 mg for the management of behavioral symptoms. The patient came for follow-up once after discharge during which small, but noticeable changes were seen in behavioral symptoms. Subsequently, the patient was lost to follow-up.


  Discussion Top


Traditionally, FTD was known to have only three types of clinical presentation, i.e., behavioral variant of FTD and the two types of PPA, i.e., the nonfluent and semantic variants, whereas ALS was considered as a Motor Neuron Disease and PSP and CBS were considered to be movement disorders. However, over the last few years, genetic studies and histopathology studies of nuclear and cytoplasmic inclusion bodies have revealed an overlap between ALS, PSP, and CBS with FTD.[5]

In the earliest reports, Tau protein inclusions called Pick Bodies were noted, and FTD was thought to be a Tauopathy. Tau depositions are seen in frontotemporal limbic/paralimbic and neocortical regions; subcortical structures like basal ganglia, locus coeruleus, and raphe nuclei; primary motor cortex and precerebellar nuclei and also in visual cortex.[6] However, recent neuropathology studies have revealed three other proteins as abnormal inclusions in FTD:

  • TDP43 protein – 43 kD transactive response DNA-binding protein[7]
  • FUS protein – fused in sarcoma (FUS) protein[8]
  • Dipeptide-repeat (DPR) protein – TDP-negative inclusions of DPR protein.[9]


TDP-43 is a RNA-binding protein. It is seen as inclusion bodies in most cases of ALS with or without FTD and FTD with or without ALS. There exists a continuum of TDP-43 proteinopathies.[10] TDP-43 appears in various abnormal morphologies including neuronal cytoplasmic inclusions, neuronal intranuclear inclusions and as neurites.[7] TDP-43 inclusion bodies can also be present in PPA, i.e., both as semantic- and nonfluent variants.

The FUS protein is a DNA and RNA-binding protein which is very similar to TDP-43 protein in function. FUS has also been reported to be associated with ALS occurring in association with bvFTD.[8]

What can be gleaned over from the above discussion is that FTD is not a single homogenous entity with a simple clinical profile caused by a single variety of inclusion body. Over the years, the clinical spectrum of FTD has expanded due to newer and more sophisticated genetic and pathological tests revealing several different genetic mutations and several different types of pathological inclusion bodies.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initial will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, et al. Frontotemporal lobar degeneration: A consensus on clinical diagnostic criteria. Neurology 1998;51:1546-54.  Back to cited text no. 1
    
2.
DeJesus-Hernandez M, Mackenzie IR, Boeve BF, Boxer AL, Baker M, Rutherford NJ, et al. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 2011;72:245-56.  Back to cited text no. 2
    
3.
Kertesz A, McMonagle P. Behavior and cognition in corticobasal degeneration and progressive supranuclear palsy. J Neurol Sci 2010;289:138-43.  Back to cited text no. 3
    
4.
Lee SE, Rabinovici GD, Mayo MC, Wilson SM, Seeley WW, DeArmond SJ, et al. Clinicopathological correlations in corticobasal degeneration. Ann Neurol 2011;70:327-40.  Back to cited text no. 4
    
5.
Josephs KA, Petersen RC, Knopman DS, Boeve BF, Whitwell JL, Duffy JR, et al. Clinicopathologic analysis of frontotemporal and corticobasal degenerations and PSP. Neurology 2006;66:41-8.  Back to cited text no. 5
    
6.
Irwin DJ, Brettschneider J, McMillan CT, Cooper F, Olm C, Arnold SE, et al. Deep clinical and neuropathological phenotyping of Pick disease. Ann Neurol 2016;79:272-87.  Back to cited text no. 6
    
7.
Davidson Y, Kelley T, Mackenzie IR, Pickering-Brown S, Du Plessis D, Neary D, et al. Ubiquitinated pathological lesions in frontotemporal lobar degeneration contain the TAR DNA-binding protein, TDP-43. Acta Neuropathol 2007;113:521-33.  Back to cited text no. 7
    
8.
Urwin H, Josephs KA, Rohrer JD, Mackenzie IR, Neumann M, Authier A, et al. FUS pathology defines the majority of tau and TDP-43-negative frontotemporal lobar degeneration. Acta Neuropathol 2010;120:33-41.  Back to cited text no. 8
    
9.
Mori K, Weng SM, Arzberger T, May S, Rentzsch K, Kremmer E, et al. The C9orf72 GGGGCC repeat is translated into aggregating dipeptide-repeat proteins in FTLD/ALS. Science 2013;339:1335-8.  Back to cited text no. 9
    
10.
Geser F, Lee VM, Trojanowski JQ. Amyotrophic lateral sclerosis and frontotemporal lobar degeneration: A spectrum of TDP-43 proteinopathies. Neuropathology 2010;30:103-12.  Back to cited text no. 10
    

Top
Correspondence Address:
Ganesh Kini,
Department of Psychiatry, Yenepoya Medical College, Deralakatte, Mangalore - 575 018, Karnataka
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/AMH.AMH_2_21





 

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