INTRODUCTION

Lafora Disease (LD) is the most common and one of severe form of adolescent-onset, progressive myoclonic epilepsies (PMEs), a group of devastating inherited neurodegenerative disorders characterized by progressively worsening myoclonus, epilepsy, early dementia and death (1). Most patients are completely normal in childhood, with the exception of early learning difficulties in some (2). The earliest symptoms are headaches, decline in school performance, spontaneous and induced myoclonus, and convulsive seizures (1).

It was reported that comorbid anxiety disorders and major depression are more common than other psychiatric disorders in epilepsy patients. Researches have shown that anxiety disorders were seen more in female patients with epilepsy, and were associated to frequency of seizures (3). Obsessive-compulsive symptoms, common anxiety symptoms, panic seizures, and panic disorder were more frequently observed in patients with epilepsy than in healthy controls (4). The risk of an anxiety disorder is higher in cases with focal epilepsy than in other cases, and also anxiety disorders occur in those with frontal lobe epilepsies and generalized epilepsies (4). However, there is no study showing how often patients with epilepsy are presented primarily with an anxiety disorder or depression.

Neuropsychiatric symptoms such as behavioral changes, depression, apathy, are also often present in LD as in other epilepsies (5). The frequency of anxiety disorders in treatment-resistant patients with epilepsy, such as patients with LD, who are scheduled for surgical treatment is 10%-44%, whereas the frequency is 11% in primary care among epileptic patients (6,7). However, it is not known definitely how often patients with epilepsy, such as LD, present with anxiety symptoms to clinics at the onset of disease. In the literature review, we could not come across with any cases with LD which presented with an anxiety disorder.

In this case, a 14-year-old female patient who presented with acute severe anxiety, and complaints of headaches, speech difficulties, decline in school performance, and whose anxiety symptoms did not improve after treatment with selective serotonin reuptake inhibitors (SSRI) is discussed. Her symptoms were followed by mutism and progressive convulsive seizures. With this case, we aimed to draw attention to differential diagnosis of underlying acute severe anxiety. Written informed consent was obtained from the patient and her family.

CASE

A 14-year-old female patient presented to Erciyes University, Faculty of Medicine, Child and Adolescent Psychiatry outpatient clinic in May 2012 with complaints of acute severe anxiety, headaches, speech difficulties and decline in school performance. She often worried that something bad would happen, had attacks which lasted about 10 minutes accompanied by sweating and palpitations twice a day and feared that she would die during an attack. She began to mispronounce letters and to stutter from time to time. She had headache accompanied by photophobia and visual hallucinations which did not responding to analgesics. Her concentration ability was decreased, so her school performance declined. Because of headaches, she could not attend school. Her complaints began suddenly in March 2012, except for headaches without any reason such as trauma. Previously, in 2008, she applied to a neurology outpatient clinic with her complaints and her preliminary diagnosis was made as migraine, so analgesic treatment was recommended. She was referred to our clinic with her family, because of increasing headache attacks and other complaints. She did not have any health problems until her complaints began. The patient and family histories were negative for mental and neurological diseases. Her blood analysis was within normal limits. The patient’s Hamilton Anxiety Rating Scale (HAM-A) score was 32 points, and she described her anxiety as varying from a feeling of tension to an intense sense of fear and panic. As she had the preliminary diagnosis of panic attacks and unspecified anxiety disorder, and also she met the criteria for generalized anxiety disorder (GAD), except for duration of disorder, treatment with escitalopram 5mg/day and lorazepam 3mg/day was started. Because her headaches did not respond to analgesics and her panic attacks continued, neurology and cardiology consultation, electroencephalography (EEG) and magnetic resonance imaging (MRI) were performed. Her cardiologic assessment was normal. The escitalopram dose was increased to 10mg/day. Her anxiety symptoms did not improve with treatment of SSRI and benzodiazepine medication after 6 weeks, her HAM-A score increased from 32 to 35 points. Her symptoms were rapidly followed by mutism and progressive convulsive seizures for two months. EEG recording showed spikes over the temporal occipital regions and photosensitivity. Brain MRI was normal. Therapy with antiepileptics caused decrease in the frequency of seizures. Adjunctive therapy with clonazepam reduced the intensity of myoclonus. However, progressive worsening of cognitive and motor functions occurred within a few months. Skin biopsy was planned for the patient who was considered as having refractory epilepsy by the neurology department. Her diagnosis was made due to the presence of polyglucosan inclusion bodies (Lafora bodies) shown in skin biopsy performed in the axilla. Lafora bodies were seen in cell types related to the sweat glands, specifically the duct cells of the eccrine glands and the myoepithelial cells surrounding apocrine glands. Also, a homozygote NHL repeat containing 1 (NHLRC1) mutation and novel homozygous epilepsy progressive myoclonus type 2A (EPM2A) mutation were detected in the patient. In the following six months, her mental decline continued without a decline resulting in severe disorientation, akinesia, hypertonia, and inability to feed, which was her clinical state prior to her admission for status epilepticus and death.

DISCUSSION

LD classically starts in adolescence in otherwise neurologically normal individuals, and usually with action and stimulus-sensitive myoclonus as well as tonic–clonic, absence, atonic, and visual seizures. The first symptoms can be dysarthria, mutism, headaches, attention deficits, depression, spontaneous and induced myoclonus, and convulsive seizures, with EEG showing background slowing and occipital-based irregular spike-wave discharges (1). The initial symptoms are followed by rapidly progressive dementia, refractory status epilepticus, psychosis, cerebellar ataxia, dysarthria, mutism, and respiratory failure which lead to death within about a decade (5,8). In our case, consistent with the literature, a 14 years old adolescent patient who was completely normal in the childhood, presented with panic attacks and GAD symptoms, and complaints of headaches, speech difficulties and decline in school performance. These initial symptoms were followed by rapidly progressive spontaneous and induced myoclonus, convulsive seizures and death.

In adults with epilepsy, depression and anxiety are the most prevalent psychiatric disorders (9). Many studies have been performed on children and adolescents with epilepsy. Ettinger et al. (10) assessed depression and anxiety with quantitative scales in a population of children and adolescents aged from 7 to 18 years with epilepsy and reported that 26% of patients had increased depression scores, and 16% had anxiety symptomatology. Oguz et al. (11) reported that adolescents with epilepsy aged between 12 and 18 years of age had higher depression and anxiety scores when compared with the control group. Dunn et al. (12) reported that 23% of 115 adolescents with epilepsy aged between 12 and 16 years had symptoms of depression. It was reported that GAD was most frequently observed in patients with epilepsy (13). Also, ictal anxiety disorders complicated severely the differential diagnosis of psychiatric diseases. Fear could occur as the only symptom of a simple partial seizure different from other ictal phenomena, and it could also be the aura of a complex partial seizure (14). There may be autonomic symptoms associated with fear during a simple partial seizure, such as palpitations, epigastric disorder, nausea, and increase in respiratory rate, paleness or flushing as in panic attacks. It was reported that patients with epilepsy who had structural lesion on the right temporal lobe were erroneously diagnosed as having panic attack disorder (15). Despite all information in the literature, it is not known definitely how often patients with epilepsy present with an anxiety disorder or depression at onset of the disorder. Our case who was presented with acute severe anxiety, met the criteria for panic attacks and also GAD except duration of the disorder before epilepsy.

The frequency of anxiety disorders in treatment-resistant epileptic patients who are scheduled for surgical treatment is 10%-44%, whereas the frequency is 11% in primary care among patients with epilepsy (6,7). Also, it is known that (4) the amygdala and right temporal focus play an important role in the formation of temporal-derived anxiety symptoms, and epileptic discharges. Some cases with complex partial status epilepticus described anxiety symptoms treated with right temporal lobectomy (16). Ictal fear was reported in about 50% of patients with epilepsy and amygdala volume was lower in patients with ictal symptoms of anxiety (4). Consistent with the literature, in our case, anxiety symptoms were not improved with treatment by SSRI, and benzodiazepines. Besides, EEG recording showed spikes over the temporal occipital regions and photosensitivity. However, the volumes of the amygdala and the temporal region were measured normal by MRI examination. It was thought that this might be due to acute onset of the disease. Also, anxiety symptoms which patient experienced before seizure initiations could be another reason.

In a conclusion, clinicians should be aware that patients who develop acute symptoms of anxiety, especially panic attacks or GAD symptoms, may have a differential diagnosis underlying anxiety. Treatment resistant patients with anxiety symptoms could have a clinical tendency for a more severe disorder including LD.

Conflict of Interest: Author declared no conflict of interest.

Financial Disclosure: Author declared no financial support.

REFERENCES

1.Monoghan TS, Delanty N. Lafora disease: epidemiology, pathophysiology and management. CNS Drugs 2010; 24:549-561. [CrossRef]

2.Franceschetti S, Gambardella A, Canafoglia L, Striano P, Lohi H, Gennaro E, Ianzano L, Veggiotti P, Sofia V, Biondi R, Striano S, Gellera C, Annesi G, Madia F, Civitelli D, Rocca FE, Quattrone A, Avanzini G, Minassian B, Zara F. Clinical and genetic findings in 26 Italian patients with Lafora disease. Epilepsia 2006; 47:640-643. [CrossRef]

3.Phabphal K, Sattawatcharawanich S, Sathirapunya P, Limapichart K. Anxiety and depression in Thai epileptic patients. J Med Assoc Thai 2007; 90:2010-2015.

4.Beyenburg S, Mitchell AJ, Schmidt D, Elger CE, Reuber M. Anxiety in patients with epilepsy: Systematic review and suggestions for clinical management. Epilepsy Behav 2005; 7:161-171. [CrossRef]

5.Ganesh S, Puri R, Singh S, Mittal S, Dubey D. Recent advances in the molecular basis of Lafora’s progressive myoclonus epilepsy. J Hum Genet 2006; 51:1-8. [CrossRef]

6.Koch-Stoecker S. Psychiatric effects of surgery for temporal lobe epilepsy: In Trimble M, Schmitz B (editors). The Neuropsychiatry of Epilepsy. Second edition. Cambridge: Cambridge University Press, 2002, 266-282. [CrossRef]

7.Trimble MR, Schmitz B. Introduction. In Trimble M, Schmitz B (editors). The Neuropsychiatry of Epilepsy. Second edition. Cambridge: Cambridge University Press, 2002, 3-17. [CrossRef]

8.El Tahry R, Tourtchaninoff M, Vrielynck P, Van Rijckevorsel K. Lafora disease: psychiatric manifestations, cognitive decline, and visual hallucinations. Acta Neurol Belg 2015; 115:471-474. [CrossRef]

9.Balıbey H, Yaşar H, Tekeli H, Bayar N. Anxiety and depression frequency in epileptic patients. Bulletin of Clinical Psychopharmacology 2015; 25:136-140.

10.Ettinger AB, Weisbrot DM, Nolan EE, Gadow KD, Vitale SA, Andriola MR Lenn NJ, Novak GP. Symptoms of depression and anxiety in pediatric epilepsy patients. Epilepsia 1998; 39:595-599. [CrossRef]

11.Oguz A, Kurul S, Dirik E. Relationship of epilepsy-related factors to anxiety and depression scores in epileptic children. J Child Neurol 2002; 17:37-40. [CrossRef]

12.Dunn DW, Austin JK, Huster GA. Symptoms of depression in adolescents with epilepsy. J Am Acad Child Adolesc Psychiatry 1999; 38:1132-1138. [CrossRef]

13.Ozmen M, Tecer O. Epilepsi Hastalarında Anksiyete ve Depresyon: In Bora I, Yeni SN, Gurses C (editors). Epilepsi. Nobel Tip Kitapevleri, 2008, 707-717. (Turkish)

14.Scicutella A. Anxiety disorders in epilepsy: In Ettinger AB, Kanner AM (editors). Psychiatric Issues Epilepsy. Lippincott Williams and Wilkins, 2001, 95-109.

15.Sazgar M, Carlen PL, Wennberg R. Panic attack semiology in right temporal epilepsy. Epileptic Disord 2003; 5:93-100.

16.McLachlan RS, Blume WT. Isolated fear in complex partial status epilepticus. Ann Neurol 1980; 8:639-641. [CrossRef]