Bravais-Jacksonian Epilepsy Associated With Type 2 Diabetes Mellitus

Introduction: Epilepsy associated with diabetes mellitus is very rare, and is seen mainly in type 1 diabetes. The focal forms are exceptional. We report an unusual observation of Bravais-Jacksonian epilepsy (BJE) in type 2 diabetes mellitus. Case report: A 50-year-old woman, who has been diabetic for a year but refuses treatment, was referred to us for high glycaemia (fasting blood glucose at 8.52 mmol/l and postprandial at 13 mmol/l) with recent onset abnormal movements in the upper left limb since a month. There were no degenerative complications of his diabetes. His HbA1C was at 8%. She was treated with metformin and intestinal alpha-glucosidase inhibitors with good evolution. The specialized neurological examination concluded with a BJE of the left arm. Brain imaging and EEG were normal. Epileptic seizures stopped after equilibration of diabetes. Conclusion: Epilepsy remains exceptional and often difficult to diagnose and treat during type 2 diabetes mellitus. Our observation is, to the best of our knowledge, the first to signal such epilepsy associated with type 2 diabetes. Citation: Bouomrani S, Regaïeg N, Belgacem N, Trabelsi S, Lassoued N, et al. Bravais-Jacksonian Epilepsy Associated With Type 2 Diabetes Mellitus. Adv Diabetes Endocrinol 2018;3(1): 3. Adv Diabetes Endocrinol 3(1): 3 (2018) Page 02 ISSN: 2475-5591 These seizures occurring during diabetes mellitus are most often symptomatic secondary to metabolic disorders specific to diabetic disease such as: hyperglycemia even without ketosis (nonketotic hyperglycaemia) [8,12,13,15,17,18], classic hypoglycaemia or exceptionally reactive hypoglycaemia hyperosmolarity or isolated hypomagnesemia [9,11,17,19-23]. More rarely, and in advanced forms of diabetes with chronic imbalance, seizures may be secondary to diabetic encephalopathy secondary to diffuse central nervous system microangiopathy (Mellitus-related encephalopathy) [10]. The association of diabetes mellitus with authentic epilepsy is much rarer, but seems far from a simple coincidence [7,24]. This association was reported with all types of diabetes mellitus: type 1 [2,4,25], type 2 [17,18,26], mitochondrial [27], Latent Autoimmune Diabetes of Adults (LADA) [28], juvenile-onset insulin-dependent diabetes and even neonatal (Permanent Neonatal Diabetes Mellitus) [29,30]. This association is more marked with type 1 diabetes where epilepsy is significantly more common than in the general population: risk multiplied by 2.8 to 3 [2,4]. This association is much rarer with type 2 diabetes; indeed only 3.35% of epileptic patients over 50 years of Ndiaye MM et al. were diabetic [26]. This prevalence, however, seems to be underestimated because in the Swedish study of 933 patients with unprovoked and newly diagnosed seizures, the odds ratio of having a seizure after the diagnosis of type 2 diabetes was 1.9 (95% CI 1.4-2.8), indicating a non-hazardous causal link compared to the general population [25]. The exact mechanism of this association is not yet well known it seems to be multifactorial, involving varying degrees of lesions of cerebral microcirculation, immunological abnormalities [13], metabolic disorders, genetic mutations and mitochondrial abnormalities [2,10,13,20,27]. In type 2 diabetics the most common clinical form of epilepsy is “Epilepsiapartialis continua” [17,18]. Epilepsy in type 2 diabetic patient remains difficult to diagnose and often represents a real diagnostic challenge for the clinician. Indeed, epilepsy may be the first manifestation of diabetes [18], and is often characterized by atypical presentations [10,15,16]. Thus, some authors recommend a systematic screening for type 2 diabetes in any patient with seizure occurring over the age of 50 [17,18]. In contrast, seizures in type 2 diabetic patients can be misinterpreted as epilepsy when they are simply symptomatic of a glycemic disorder that must be objectified, sometimes even through continuous glucose monitoring [11]. The seizures/epilepsies associated with diabetes mellitus are classically resistant to anticonvulsant therapy and respond better to insulin with rehydration [12,18], and insulin may be the only medication neededto treat effectively these cases [14]. Conclusion Epilepsy is exceptionally associated with type 2 diabetes. It represents a real diagnostic and therapeutic challenge for the clinician, because of these often atypical clinical presentations, it’s resistance to anticonvulsants, and the differential diagnosis problem with simple symptomatic seizures secondary to glycemic disorder, not always easy to solve. Our observation is, to our knowledge, the first reporting the association of a focal epilepsy type Bravais-Jacksonian to type 2 diabetes mellitus. The causal link is comforted by the concomitant appearance with the uncontrolled diabetes, normality of radiological and electrical neurological investigations, and the disappearance of seizures with the correction of glycemic parameters even after stopping the anticonvulsant treatment. References 1. Bouomrani S, Ben Hamed M, Regaïeg N, Belgacem N, Baïli H, et al. (2018) Bilateral Retrobulbar Optic Neuritis Revealing Type 1 Diabetes Mellitus. EC Neurology 10.6: 446-449. 2. Chou IC, Wang CH, Lin WD, Tsai FJ, Lin CC, et al. (2016) Risk of epilepsy in type 1 diabetes mellitus: a population-based cohort study. Diabetologia 59: 1196-1203. 3. Obata A, Kutoku Y, Sunada Y, Okauchi S, Kimura T, et al. (2017) Temporal lobe epilepsy associated with GAD autoimmunity. Acta Diabetol 54: 321-323. 4. Dafoulas GE, Toulis KA, Mccorry D, Kumarendran B, Thomas GN, et al. (2017) Type 1 diabetes mellitus and risk of incident epilepsy: a populationbased, open-cohort study. Diabetologia 60: 258-261. 5. Keezer MR, Novy J, Sander JW (2015) Type 1 diabetes mellitus in people with pharmacoresistant epilepsy: Prevalence and clinical characteristics. Epilepsy Res 115: 55-57. 6. Falip M, Miró J, Carreño M, Jaraba S, Becerra JL, et al. (2014) Hypoglycemic seizures and epilepsy in type I diabetes mellitus. J Neurol Sci 346: 307-309. 7. Yun C, Xuefeng W (2013) Association between seizures and diabetes mellitus: a comprehensive review of literature. Curr Diabetes Rev 9: 350-354. 8. Trimeche S, Chadli-Chaieb M, Maaroufi A, Ach K, Chaieb L (2003) Hyperglycemic seizure in diabetic patient. Report of five cases. Rev Med Interne 24: 270-271. 9. Lambrinoudakis N, Glanzmann MC, Franzen D (2008) Bilateral fractures of the humerus after hypoglycemic seizure. Dtsch Med Wochenschr 133: 884886. 10. Kashihara K, Shohmori T, Otsuki S (1997) Noninsulin-dependent diabetes mellitus-related encephalopathy presenting with amnesia, personality change, and autonomic seizure. Intern Med 36: 633-636. 11. Monami M, Mannucci E, Breschi A, Marchionni N (2005) Seizures as the only clinical manifestation of reactive hypoglycemia: a case report. J Endocrinol Invest 28: 940-941. 12. Donat A, Guilloton L, Bonnet C, Depreux G, Lamboley JL, et al. Partial visual seizures induced by non-ketosic hyperglycemia: magnetic resonance imaging and visual evoked potential descriptions. A study of two cases reports with radiologic and electrophysiologic abnormalities. Rev Neurol (Paris) 169: 154161. 13. Conduit C, Harle R, Jones DL (2016) Non-ketotic hyperglycaemia causing occipital seizures and persistent microhaemorrhages: mechanisms of focal deficits in hyperglycaemia. Intern Med J 46: 634-635. 14. Mak KH, Chee M (1990) Focal seizure in non-ketotic hyperglycaemia. Ann Acad Med Singapore 19: 556-558. 15. Carril JM, Guijarro C, Portocarrero JS, Solache I, Jiménez A, et al. (1992) Speech arrest as manifestation of seizures in non-ketotic hyperglycaemia. Lancet 340: 1227. 16. Tiamkao S, Pratipanawatr T, Jitpimolmard S (2011) Abdominal epilepsy: an uncommon of non-convulsive status epilepticus. J Med Assoc Thai 94: 9981001. 17. Hennis A, Corbin D, Fraser H (1992) Focal seizures and non-ketotic Citation: Bouomrani S, Regaïeg N, Belgacem N, Trabelsi S, Lassoued N, et al. Bravais-Jacksonian Epilepsy Associated With Type 2 Diabetes Mellitus. Adv Diabetes Endocrinol 2018;3(1): 3. Adv Diabetes Endocrinol 3(1): 3 (2018) Page 03 ISSN: 2475-5591 hyperglycaemia. J Neurol Neurosurg Psychiatry 55: 195-197. 18. Scherer C (2005) Seizures and non-ketotic hyperglycemia. Presse Med 34: 1084-1086. 19. Lin YY, Hsu CW, Sheu WH, Chu SJ, Wu CP, et al. (2010) Risk factors for recurrent hypoglycemia in hospitalized diabetic patients admitted for severe hypoglycemia. Yonsei Med J 51: 367-374. 20. Khan U, Seetharaman S, Merchant R (2017) Neuroglycopenic Seizures: Sulfonylureas, Sulfamethoxazole, or Both? Am J Med 130: e29-e30. 21. Bhagwat NM, Joshi AS, Rao G, Varthakavi PK (2013) Uncontrolled hyperglycaemia: a reversible cause of hemichorea-hemiballismus. BMJ Case Rep 2013. pii: bcr2013010229. 22. Price A, Losek J, Jackson B (2016) Hyperglycaemic hyperosmolar syndrome in children: Patient characteristics, diagnostic delays and associated complications. J Paediatr Child Health 52: 80-84. 23. Matthey F, Gelder CM, Schon FE (1986) Isolated hypomagnesaemia presenting as focal seizures in diabetes mellitus. Br Med J (Clin Res Ed) 293: 1409. 24. Mancardi MM, Striano P, Giannattasio A, Baglietto MG, Errichiello L, et al. (2010) Type 1 diabetes and epilepsy: more than a casual association? Epilepsia 51: 320-321. 25. Adelöw C, Andersson T, Ahlbom A, Tomson T (2011) Prior hospitalization for stroke, diabetes, myocardial infarction, and subsequent risk of unprovoked seizures. Epilepsia 52: 301-307. 26. Ndiaye MM, Diagana M, Diop AG, Thiam A, Diagne M, et al. (1990) Epilepsy detected in diabetes in patients over 50 years. Dakar Med 35: 120-125. 27. Bouhanick B, Reynier P, Salle A, Ilhouz F, Coutant R, et al. (2002) West syndrome and mitochondrial diabetes: relationship or coincidence? Clin Endocrinol (Oxf) 57: 142-144. 28. Soós Z, Salamon M, Erdei K, Kaszás N, Folyovich A, et al. (2014) LADA type diabetes, celiac diasease, cerebellar ataxia and stiff person syndrome. A rare association of autoimmune disorders. Ideggyogy Sz 67: 205-209. 29. Sanyoura M, Woudstra C, Halaby G, Baz P, Senée V, et al. (2014) A novel ALMS1 splice mutation in a non-obese juvenile-onsetinsulin-dependent syndromic diabetic patient. Eur J Hum Genet 22: 140-143. 30. Singh P, Rao SC, Parikh R (2014) Neonatal diabetes with intractable epilepsy: DEND syndrome. Indian J Pediatr 81: 1387-1388.


Introduction
The neurological manifestations during diabetes mellitus are varied and often the prerogative of old and unbalanced forms, however inaugural forms can be seen [1]. Peripheral neuropathies are by far the most common (60% of diabetics at some point in the course of the disease) whereas seizures are much rarer, and are mainly seen in type 1 diabetes [2][3][4].
In addition, a potential association between authentic epilepsy and diabetes mellitus is strongly evoked; it is particularly clear with type 1diabetes and it has been demonstrated an epileptogenic physio pathogenetic promoting role of anti-Glutamic Acid Decarboxylase (anti-GAD) autoantibodies, particularly in the genesis of temporal epilepsy [2,5,6]. These forms of epilepsy are classified as "autoimmune epilepsy" [6].
In diabetes mellitus type 2, epilepsy is much rarer, and is most often symptomatic (secondary to an underlying cause), unlike type 1 diabetes, where it is most often cryptogenic/primitive (85% versus 35%) [5].
We report an unusual observation of focal epilepsy type Bravais-Jacksonian in type 2 diabetes mellitus; an association that, to our knowledge, has not been reported before.

Case Report
A 50-year-old woman, who has been diabetic 2 for a year but refuses treatment, was referred to us for high glycaemias (fasting blood glucose at 8.52 mmol/l and postprandial at 13 mmol/l) with recent onset of abnormal movements in the upper left limb since a month.
There were no degenerative complications of his diabetes: 24-hour blood pressure profile, electrocardiogram, chest X-ray, creatinine and glomerular filtration rate, microalbuminumia and 24-hour urinary protein, ophthalmological examination and fundus were without anomalies. The Glycosylated Hemoglobin (HbA1C) was at 8%.
She was treated with metformin (2000 mg/d) and intestinal alphaglucosidase inhibitors (150 mg/d) with a good evolution.
The specialized neurological examination concluded toBravais-Jacksonian epilepsy of the left arm. Neurological imaging (cerebral CT, cerebral MRI and angio-MR) and electroencephalogram were without abnormalities. The electromyogram did not show signs of diabetic peripheral neuropathy in all four limbs.
She was initially treated with carbamazepine at a dose of 200 mg/ day to stop seizures.
After three months, her glycemic control was satisfactory: fasting glucose at 5.2 mmol/ l,2 h postprandial glucose at 10 mmol/l and HbA1C at 6.5%. Carbamazepine was stopped and no recurrence of seizures was noted for now three years.
More rarely, and in advanced forms of diabetes with chronic imbalance, seizures may be secondary to diabetic encephalopathy secondary to diffuse central nervous system microangiopathy (Mellitus-related encephalopathy) [10].
This association is more marked with type 1 diabetes where epilepsy is significantly more common than in the general population: risk multiplied by 2.8 to 3 [2,4]. This association is much rarer with type 2 diabetes; indeed only 3.35% of epileptic patients over 50 years of Ndiaye MM et al. were diabetic [26]. This prevalence, however, seems to be underestimated because in the Swedish study of 933 patients with unprovoked and newly diagnosed seizures, the odds ratio of having a seizure after the diagnosis of type 2 diabetes was 1.9 (95% CI 1.4-2.8), indicating a non-hazardous causal link compared to the general population [25].
The exact mechanism of this association is not yet well known it seems to be multifactorial, involving varying degrees of lesions of cerebral microcirculation, immunological abnormalities [13], metabolic disorders, genetic mutations and mitochondrial abnormalities [2,10,13,20,27].
In type 2 diabetics the most common clinical form of epilepsy is "Epilepsiapartialis continua" [17,18].
Epilepsy in type 2 diabetic patient remains difficult to diagnose and often represents a real diagnostic challenge for the clinician. Indeed, epilepsy may be the first manifestation of diabetes [18], and is often characterized by atypical presentations [10,15,16]. Thus, some authors recommend a systematic screening for type 2 diabetes in any patient with seizure occurring over the age of 50 [17,18].
In contrast, seizures in type 2 diabetic patients can be misinterpreted as epilepsy when they are simply symptomatic of a glycemic disorder that must be objectified, sometimes even through continuous glucose monitoring [11].
The seizures/epilepsies associated with diabetes mellitus are classically resistant to anticonvulsant therapy and respond better to insulin with rehydration [12,18], and insulin may be the only medication neededto treat effectively these cases [14].

Conclusion
Epilepsy is exceptionally associated with type 2 diabetes. It represents a real diagnostic and therapeutic challenge for the clinician, because of these often atypical clinical presentations, it's resistance to anticonvulsants, and the differential diagnosis problem with simple symptomatic seizures secondary to glycemic disorder, not always easy to solve.
Our observation is, to our knowledge, the first reporting the association of a focal epilepsy type Bravais-Jacksonian to type 2 diabetes mellitus. The causal link is comforted by the concomitant appearance with the uncontrolled diabetes, normality of radiological and electrical neurological investigations, and the disappearance of seizures with the correction of glycemic parameters even after stopping the anticonvulsant treatment.