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Dementia as presenting symptom of primary hyperparathyroidism: Favourable outcome after surgery
Clinical Neurology and Neurosurgery 110 (2008) 1038–1040
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Case report
Dementia as presenting symptom of primary hyperparathyroidism: Favourable outcome after surgery Sokratis G. Papageorgiou ∗ , Yolanda Christou, Theodoros Kontaxis, Anastasios Bonakis, Maria Anagnostouli, Constantinos Potagas, Nikolaos Kalfakis Department of Neurology, Athens University Medical School, Eginition Hospital, Athens, Greece
a r t i c l e
i n f o
Article history: Received 25 January 2008 Received in revised form 20 May 2008 Accepted 14 June 2008 Keywords: Primary hyperparathyroidism Cognitive deficit Dementia Parathyroidectomy
a b s t r a c t The case of a 76-year-old female patient is presented with a two-year history of progressive dementia, apathy and gait impairment. Initially, Alzheimer’s disease was diagnosed and she was given donepezil for one year with no significant improvement. An extensive blood and biochemical control revealed high serum calcium and parathormone levels, and normal thyroid hormones and anti-thyroid antibodies. Ultrasound of thyroid and parathyroid glands revealed an adenoma of the right parathyroid. The detailed investigation for causes of secondary hyperparathyroidism was negative. Due to the absence of clinical hyperparathyroidism she was initially treated conservatively. At referral, the neurological picture consisted of: mild signs of parkinsonism, moderate dementia (MMSE = 15) and severe behavioural disturbances. Because of the continuous aggravation of the cognitive deficit, parathyroidectomy was decided although there were no clinical or laboratory signs of involvement from other organs. Three weeks after the operation the neurological picture showed dramatical improvement. Parkinsonism and behavioural disorders were remarkably reduced and the MMSE score raised to 25. In summary we report an exceptional case of primary hyperparathyroidism (PHPT) presenting as dementia and treated successfully by parathyroidectomy. © 2008 Elsevier B.V. All rights reserved.
1. Introduction Primary hyperparathyroidism (PHPT) involves primarily the kidneys and the skeletal system. In symptomatic patients, dysfunction of the CNS, peripheral nerve and muscle, gastrointestinal tract and joints may occur. Dementia as presenting symptom of PHPT is extremely rare with only few published cases in the literature [1,2]. We report an exceptional case of a 76-year-old woman with primary hyperparathyroidism presenting as dementia, which reversed after parathyroidectomy. 2. Case report The patient was a 76-year-old female who presented with progressive dementia with memory impairment, cognitive deficit (especially concentration and attention), apathy and gait impairment. Her medical history consisted of arterial hypertension, for
∗ Corresponding author at: Department of Neurology, Eginition Hospital, University of Athens, 74, Vassilissis Sofias Avenue, 11528 Athens, Greece. Tel.: +30 2107289404; fax: +30 2107216474. E-mail address: [email protected] (S.G. Papageorgiou). 0303-8467/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.clineuro.2008.06.004
which she was taking diuretics, and osteoporosis. She had one normal delivery and went into menopause at the age of 40. There was no history of allergies or alcohol abuse. She had quit smoking three years previously. She had a sister with hypercalcemia and a nephew with renal colic. Her symptoms had begun two years previously with withdrawal, clinophilia and apathy, as well as deficit in concentration and communication. At that time her Mini Mental State Examination (MMSE) score was 25/30. She was diagnosed as suffering from Alzheimer’s disease and started treatment with donepezil for one year with no significant improvement. One year previously she had a fracture of the left brachiocarpal joint that was attributed to osteoporosis relative to her age. Since then her symptomatology aggravated. Due to clinophilia she developed deep vein thrombosis of the left leg which was treated with anticoagulants. Three months prior to admission she was hospitalized with a TIA, presenting with right hemiparesis which resolved totally. Upon arrival to our clinic the neurological picture consisted of: mild parkinsonism with tremor and rigidity of the upper extremities, gait impairment-abasia (unable to walk without help), severe behavioural disturbances and moderate dementia with a MMSE score of 15/30. The Clinical Dementia Rate (CDR) sum of boxes was 14, stage 2 (range from 0 to 3). The Neuropsychiatric Inven-
S.G. Papageorgiou et al. / Clinical Neurology and Neurosurgery 110 (2008) 1038–1040
tory (NPI) total score was 52 (scores in NPI range from 0 to 144, with 0 indicating normal behaviour, and 144, indicating severe behavioural disturbances). Her most marked behavioural disturbances included: severe apathy, disturbances of sleep (insomnia during the night, excessive sleep during daytime), excessive food consumption, motor stereotypies and automatisms. The Frontal Behavioral Inventory (FBI) score was 45, due to deficits in practically all fields assessed (apathy, lack of initiative, neglect of personal hygiene, disorganization, lack of insight etc). (FBI scores range from 0 to 72, 0 = normal, 72 = severe behavioral disturbances.) She was almost fully depended in everyday activities. The Instrumental Activities of Daily Living Scale (IADL) score was 31. (In this scale 8 indicating no functional impairment in activities of daily living, maximum number 31.) The brain magnetic resonance imaging revealed mild cortical atrophy and a few nonspecific hyperintensive lesions periventricularly. The CSF examination showed no cells, normal protein and glucose and presence of oligoclonal bands with slightly elevated IgG index. All standard haematological and biochemical laboratory tests including a complete blood count, serum electrolytes, blood sugar, acute C-reactive protein, liver function test, blood urea nitrogen, serum cholesterol, lipid levels and treponemal serology were within normal range, apart from raised serum calcium (11.7 mg/dl), raised ionized calcium (5.03), low serum phosphorus (2.21 mg/dl) and high parathormone (PTH) (7.5 pg/ml). The urine calcium was normal. An ultrasound and a scintigraphy of thyroid and parathyroid glands revealed an adenoma of the right parathyroid gland and a nodular morphology of the thyroid gland. The thyroid hormones and anti-thyroid antibodies levels were normal. A detailed investigation for causes of secondary hyperparathyroidism was negative. In addition, there was no evidence, of neonatal or infantile hyperparathyroidism in her family suggesting familial hypocalciuric hypercalcemia. The comprehensive clinical, neuropsychological, behavioral, laboratory and imaging investigation, did not reveal specific features of Alzheimer’s disease, or other primary degenerative dementia. Because of the absence of symptoms of hyperparathyroidism from other systems (renal, gastrointestinal, and skeletal system) and moderate hypercalcemia, she was initially treated conservatively with a low calcium diet and good hydration. However, because of the continuing deterioration of her cognitive and behavioral status and in view of the absence of evidence for other dementing disease either primary or secondary, surgical treatment with parathyroidectomy was decided even in the absence of other organic signs of PHPT (see Section 3 for details). Although, this matter is controversial, two recent studies (5, 6) have shown that surgical treatment appears to improve cognitive symptoms in patients with PHPT. A subtotal parathyroidectomy was performed and the biopsy of the parathyroid glands showed hyperplasia of parathyroid glands with no signs of malignancy. Three weeks after the operation the neurological examination showed dramatical improvement with a MMSE score of 23/30, a CDR sum of boxes 11 (stage 2), NPI score of 21 (apathy and distur-
1039
bances of sleep), IADL score 29, FBI 25 and FAB (Frontal Assessment Battery) 10/18. At that time, the Geriatric Depression Scale score was 3 (0 = indicating no depression, maximum score number = 15). Her motor function also improved and she was once again able to stand alone and walk with help. The serum level of calcium was 9.7 mg/dl, phosphorus 3.6 mg/dl and PTH 14.6 pg/ml. Three months later the patient could walk on her own, she had a MMSE score of 23/30, CDR sum of boxes 7.5 (stage 1), NPI score was only 3 (apathy, stress, and sleep disorders), IADL = 25 and FAB = 8/18. At the final evaluation 4 months after parathyroidectomy she showed further improvement of gait and motility in general with a MMSE score of 26/30, CDR sum of boxes 6 (stage 1), NPI 12 (apathy, stress, diet disturbances), IADL 20, FBI 18 and FAB 13/18.
3. Discussion Primary hyperparathyroidism is a common endocrine disorder, affecting predominantly postmenopausal women [4] and is characterized as a disease of “bones, stones and psychic groans”. It is a disorder of calcium, phosphate and bone metabolism due to an increased secretion of PTH resulting to hypercalcemia and hypophosphatemia. The disease involves primarily the kidney (deposition of calcium in the renal parenchyma or recurrent nephrolithiasis) the skeletal system (osteitis fibrosa cystica), the gastrointestinal tract (peptic ulcer and pancreatitis). Dysfunction of CNS, peripheral nerve and muscles has been reported in symptomatic patients. In the case of our patient the classical symptoms were absent and clinical picture at presentation was a severe cognitive deficit. Asymptomatic PHPT presenting as dementia seems to be extremely rare with only two published cases in the literature [1,2]. Another unusual aspect of our case is the rapidity of the remarkable improvement post parathyroidectomy at all levels: movement, memory, attention, concentration, and general quality of life (see also Table 1). The specific biochemical mechanism responsible for the development of dementia in PHPT is unknown. There may be an influence of calcium metabolism on higher cortical functioning [5]. Hypercalcemia associated with PHPT has been linked to mild neurologic changes, including personality alteration and depression. More severe hypercalcemia potentially results in confusion, psychosis, coma or even death. Joborn et al. [7] have found that patients with PHPT have increased CSF concentrations of both total and ionized calcium, as a consequence of the increased serum calcium level and the impaired blood–brain barrier function (possibly related to the influence of serum PTH). In addition the high CSF calcium concentration is likely to affect brain function. A brain imaging functional study has demonstrated significantly reduced regional cerebral blood flow in cingulate cortex, superior and inferior frontal cortex bilaterally, anterior temporal cortex, precentral gyrus, postcentral gyrus and pariental cortex [10].
Table 1 Neuropsychological evaluation prior and post parathyroidectomy
MMSE CDR NPI IADL FBI FAB
1 month prior parathyroidectomy
3 weeks after parathyroidectomy
3 months after parathyroidectomy
4 months after parathyroidectomy
15 Sum of boxes 14, stage 2 52 32 45
23 Sum of boxes 11, stage 2 21 29 25 7
23 Sum of boxes 7.5, stage 1 12 25 – 10
26 Sum of boxes, 6 stage 1 12 22 18 13
MMSE: Mini Mental State Examination, CDR: Clinical Dementia Rate, NPI: Neuropsychological Inventory, IADL: Instrumental Activities of Daily Living Scale, FBI: Frontal Behavioral Inventory, FBI: Frontal Assessment Battery.
1040
S.G. Papageorgiou et al. / Clinical Neurology and Neurosurgery 110 (2008) 1038–1040
Hypoperfusion in these cortical areas was correlated with serum calcium and PTH levels. In two prospective studies of functional imaging, with SPECT [1] and fMRI [1], frontal reduced cerebral blood flow was found to be improved after parathyroidectomy, together with cognitive amelioration. There is a disagreement whether asymptomatic PHPT should be managed conservatively with surveillance, or with an early parathyroidectomy. According to the guidelines of the National Institutes of Health (NIH) for the management of asymptomatic PHPT [8,9], neurocognitive factors are integral to the diagnosis and treatment of PHPT, but should not constitute the sole indication for surgery. Some recent studies on the effect of surgery on cognitive symptoms in patients with PHPT showed that there was no significant improvement in cognitive deficits after successful parathyroidectomy [13,14,15]. However, other studies showed that surgical treatment appeared to improve some of these symptoms and afford benefit to the patients, quality of life [5,6,11]. The remarkable improvement of our patient post parathyroidectomy at all levels (Table 1) favours early parathyroidectomy in cases of PHPT with significant complications from CNS even in the absence of other symptoms of PHPT. In addition, our case suggests that, although rare, asymptomatic PHPT should be considered as a possible cause of dementia. References [1] Molaschi M, Ponzetto M, Romin R, et al. Neuropsychologic symptoms of primary hyperparathyroidism in the elderly. Report of a clinical case. Minerva Endocrinologica 1994;19:169–74.
[2] Joborn C, Hetta J, Frisk P, Palmer M, Akerstrom G, Ljunghall S. Primary hyperparathyroidism in patients with organic brain syndrome. Acta Medica Scandinavia 1986;219:91–8. [4] Silverberg SJ, Bilezikian JP. The diagnosis and management of asymptomatic primary hyperparathyroidism. Endocrinology & Metabolism 2006;2:494– 503. [5] Roman SA, Sosa JA, Mayes L, et al. Parathyroidectomy improves neurocognitive deficit in patients with primary hyperparathyroidism. Surgery 2005;138:1121–9. [6] Roman SA, Sosa JA. Psychiatric and cognitive aspects of primary hyperparathyroidism. Current Opinion in Oncology 2007;19:1–5. [7] Joborn C, Hetta J, Niklasson F, et al. Cerbrospinal fluid calcium, parathyroid hormone, and monoamine and purine metabolites and the blood–brain barrier function in primary hyperparathyroidism. Psychoneuroendocrinology 1991;16:311–22. [8] Cermik TF, Kaya M, Ugur-Altun B, et al. Regional cerebral blood flow abnormalities in patients with primary hyperparathyroidism. Neuroradiology 2007;49:379–85. [9] Mjaland O, Normann E, Halvorsen E, et al. Regional cerebral blood flow in patients with primary hyperparathyroidism before and after successful parathyroidectomy. British Journal of Surgery 2003;90:732–7. [10] Perrier ND, Coker LH, Rorie KD, et al. Preliminary report: functional MRI of the brain may be the ideal tool for evaluating neuropsychologic and sleep complaints of patients with primary hyperparathyroidism. World Journal of Surgery 2006;30:686–96. [11] Potts Jr JT, Fradkin JE, Aurbach GD, et al., editors. Proceedings of the NIH Consensus Development Conference on Diagnosis and Management of Asymptomatic Primary Hyperparathyroidism. J Bone Miner Res 1991;6:S1–166. [13] Prager G, Kalashek A, Kaczirek K, et al. Parathyroidectomy improved cognition and retentiveness in patients with primary hyperparathyroidism. Surgery 2002;132:930–6. [14] Dotzenrath CM, Kaetsch AK, Pfingsten H, et al. Neuropsychiatric and cognitive changes after surgery for primary hyperparathyroidism. World Journal of Surgery 2006;30:680–5. [15] Chiang CY, Andrewest DG, Anderson D, et al. A controlled, prospective study of neuropsychological outcomes post parathyroidectomy in primary hyperparathyroid patients. Clinical Endocrinology 2005;62:99–104.
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Case report
Dementia as presenting symptom of primary hyperparathyroidism: Favourable outcome after surgery Sokratis G. Papageorgiou ∗ , Yolanda Christou, Theodoros Kontaxis, Anastasios Bonakis, Maria Anagnostouli, Constantinos Potagas, Nikolaos Kalfakis Department of Neurology, Athens University Medical School, Eginition Hospital, Athens, Greece
a r t i c l e
i n f o
Article history: Received 25 January 2008 Received in revised form 20 May 2008 Accepted 14 June 2008 Keywords: Primary hyperparathyroidism Cognitive deficit Dementia Parathyroidectomy
a b s t r a c t The case of a 76-year-old female patient is presented with a two-year history of progressive dementia, apathy and gait impairment. Initially, Alzheimer’s disease was diagnosed and she was given donepezil for one year with no significant improvement. An extensive blood and biochemical control revealed high serum calcium and parathormone levels, and normal thyroid hormones and anti-thyroid antibodies. Ultrasound of thyroid and parathyroid glands revealed an adenoma of the right parathyroid. The detailed investigation for causes of secondary hyperparathyroidism was negative. Due to the absence of clinical hyperparathyroidism she was initially treated conservatively. At referral, the neurological picture consisted of: mild signs of parkinsonism, moderate dementia (MMSE = 15) and severe behavioural disturbances. Because of the continuous aggravation of the cognitive deficit, parathyroidectomy was decided although there were no clinical or laboratory signs of involvement from other organs. Three weeks after the operation the neurological picture showed dramatical improvement. Parkinsonism and behavioural disorders were remarkably reduced and the MMSE score raised to 25. In summary we report an exceptional case of primary hyperparathyroidism (PHPT) presenting as dementia and treated successfully by parathyroidectomy. © 2008 Elsevier B.V. All rights reserved.
1. Introduction Primary hyperparathyroidism (PHPT) involves primarily the kidneys and the skeletal system. In symptomatic patients, dysfunction of the CNS, peripheral nerve and muscle, gastrointestinal tract and joints may occur. Dementia as presenting symptom of PHPT is extremely rare with only few published cases in the literature [1,2]. We report an exceptional case of a 76-year-old woman with primary hyperparathyroidism presenting as dementia, which reversed after parathyroidectomy. 2. Case report The patient was a 76-year-old female who presented with progressive dementia with memory impairment, cognitive deficit (especially concentration and attention), apathy and gait impairment. Her medical history consisted of arterial hypertension, for
∗ Corresponding author at: Department of Neurology, Eginition Hospital, University of Athens, 74, Vassilissis Sofias Avenue, 11528 Athens, Greece. Tel.: +30 2107289404; fax: +30 2107216474. E-mail address: [email protected] (S.G. Papageorgiou). 0303-8467/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.clineuro.2008.06.004
which she was taking diuretics, and osteoporosis. She had one normal delivery and went into menopause at the age of 40. There was no history of allergies or alcohol abuse. She had quit smoking three years previously. She had a sister with hypercalcemia and a nephew with renal colic. Her symptoms had begun two years previously with withdrawal, clinophilia and apathy, as well as deficit in concentration and communication. At that time her Mini Mental State Examination (MMSE) score was 25/30. She was diagnosed as suffering from Alzheimer’s disease and started treatment with donepezil for one year with no significant improvement. One year previously she had a fracture of the left brachiocarpal joint that was attributed to osteoporosis relative to her age. Since then her symptomatology aggravated. Due to clinophilia she developed deep vein thrombosis of the left leg which was treated with anticoagulants. Three months prior to admission she was hospitalized with a TIA, presenting with right hemiparesis which resolved totally. Upon arrival to our clinic the neurological picture consisted of: mild parkinsonism with tremor and rigidity of the upper extremities, gait impairment-abasia (unable to walk without help), severe behavioural disturbances and moderate dementia with a MMSE score of 15/30. The Clinical Dementia Rate (CDR) sum of boxes was 14, stage 2 (range from 0 to 3). The Neuropsychiatric Inven-
S.G. Papageorgiou et al. / Clinical Neurology and Neurosurgery 110 (2008) 1038–1040
tory (NPI) total score was 52 (scores in NPI range from 0 to 144, with 0 indicating normal behaviour, and 144, indicating severe behavioural disturbances). Her most marked behavioural disturbances included: severe apathy, disturbances of sleep (insomnia during the night, excessive sleep during daytime), excessive food consumption, motor stereotypies and automatisms. The Frontal Behavioral Inventory (FBI) score was 45, due to deficits in practically all fields assessed (apathy, lack of initiative, neglect of personal hygiene, disorganization, lack of insight etc). (FBI scores range from 0 to 72, 0 = normal, 72 = severe behavioral disturbances.) She was almost fully depended in everyday activities. The Instrumental Activities of Daily Living Scale (IADL) score was 31. (In this scale 8 indicating no functional impairment in activities of daily living, maximum number 31.) The brain magnetic resonance imaging revealed mild cortical atrophy and a few nonspecific hyperintensive lesions periventricularly. The CSF examination showed no cells, normal protein and glucose and presence of oligoclonal bands with slightly elevated IgG index. All standard haematological and biochemical laboratory tests including a complete blood count, serum electrolytes, blood sugar, acute C-reactive protein, liver function test, blood urea nitrogen, serum cholesterol, lipid levels and treponemal serology were within normal range, apart from raised serum calcium (11.7 mg/dl), raised ionized calcium (5.03), low serum phosphorus (2.21 mg/dl) and high parathormone (PTH) (7.5 pg/ml). The urine calcium was normal. An ultrasound and a scintigraphy of thyroid and parathyroid glands revealed an adenoma of the right parathyroid gland and a nodular morphology of the thyroid gland. The thyroid hormones and anti-thyroid antibodies levels were normal. A detailed investigation for causes of secondary hyperparathyroidism was negative. In addition, there was no evidence, of neonatal or infantile hyperparathyroidism in her family suggesting familial hypocalciuric hypercalcemia. The comprehensive clinical, neuropsychological, behavioral, laboratory and imaging investigation, did not reveal specific features of Alzheimer’s disease, or other primary degenerative dementia. Because of the absence of symptoms of hyperparathyroidism from other systems (renal, gastrointestinal, and skeletal system) and moderate hypercalcemia, she was initially treated conservatively with a low calcium diet and good hydration. However, because of the continuing deterioration of her cognitive and behavioral status and in view of the absence of evidence for other dementing disease either primary or secondary, surgical treatment with parathyroidectomy was decided even in the absence of other organic signs of PHPT (see Section 3 for details). Although, this matter is controversial, two recent studies (5, 6) have shown that surgical treatment appears to improve cognitive symptoms in patients with PHPT. A subtotal parathyroidectomy was performed and the biopsy of the parathyroid glands showed hyperplasia of parathyroid glands with no signs of malignancy. Three weeks after the operation the neurological examination showed dramatical improvement with a MMSE score of 23/30, a CDR sum of boxes 11 (stage 2), NPI score of 21 (apathy and distur-
1039
bances of sleep), IADL score 29, FBI 25 and FAB (Frontal Assessment Battery) 10/18. At that time, the Geriatric Depression Scale score was 3 (0 = indicating no depression, maximum score number = 15). Her motor function also improved and she was once again able to stand alone and walk with help. The serum level of calcium was 9.7 mg/dl, phosphorus 3.6 mg/dl and PTH 14.6 pg/ml. Three months later the patient could walk on her own, she had a MMSE score of 23/30, CDR sum of boxes 7.5 (stage 1), NPI score was only 3 (apathy, stress, and sleep disorders), IADL = 25 and FAB = 8/18. At the final evaluation 4 months after parathyroidectomy she showed further improvement of gait and motility in general with a MMSE score of 26/30, CDR sum of boxes 6 (stage 1), NPI 12 (apathy, stress, diet disturbances), IADL 20, FBI 18 and FAB 13/18.
3. Discussion Primary hyperparathyroidism is a common endocrine disorder, affecting predominantly postmenopausal women [4] and is characterized as a disease of “bones, stones and psychic groans”. It is a disorder of calcium, phosphate and bone metabolism due to an increased secretion of PTH resulting to hypercalcemia and hypophosphatemia. The disease involves primarily the kidney (deposition of calcium in the renal parenchyma or recurrent nephrolithiasis) the skeletal system (osteitis fibrosa cystica), the gastrointestinal tract (peptic ulcer and pancreatitis). Dysfunction of CNS, peripheral nerve and muscles has been reported in symptomatic patients. In the case of our patient the classical symptoms were absent and clinical picture at presentation was a severe cognitive deficit. Asymptomatic PHPT presenting as dementia seems to be extremely rare with only two published cases in the literature [1,2]. Another unusual aspect of our case is the rapidity of the remarkable improvement post parathyroidectomy at all levels: movement, memory, attention, concentration, and general quality of life (see also Table 1). The specific biochemical mechanism responsible for the development of dementia in PHPT is unknown. There may be an influence of calcium metabolism on higher cortical functioning [5]. Hypercalcemia associated with PHPT has been linked to mild neurologic changes, including personality alteration and depression. More severe hypercalcemia potentially results in confusion, psychosis, coma or even death. Joborn et al. [7] have found that patients with PHPT have increased CSF concentrations of both total and ionized calcium, as a consequence of the increased serum calcium level and the impaired blood–brain barrier function (possibly related to the influence of serum PTH). In addition the high CSF calcium concentration is likely to affect brain function. A brain imaging functional study has demonstrated significantly reduced regional cerebral blood flow in cingulate cortex, superior and inferior frontal cortex bilaterally, anterior temporal cortex, precentral gyrus, postcentral gyrus and pariental cortex [10].
Table 1 Neuropsychological evaluation prior and post parathyroidectomy
MMSE CDR NPI IADL FBI FAB
1 month prior parathyroidectomy
3 weeks after parathyroidectomy
3 months after parathyroidectomy
4 months after parathyroidectomy
15 Sum of boxes 14, stage 2 52 32 45
23 Sum of boxes 11, stage 2 21 29 25 7
23 Sum of boxes 7.5, stage 1 12 25 – 10
26 Sum of boxes, 6 stage 1 12 22 18 13
MMSE: Mini Mental State Examination, CDR: Clinical Dementia Rate, NPI: Neuropsychological Inventory, IADL: Instrumental Activities of Daily Living Scale, FBI: Frontal Behavioral Inventory, FBI: Frontal Assessment Battery.
1040
S.G. Papageorgiou et al. / Clinical Neurology and Neurosurgery 110 (2008) 1038–1040
Hypoperfusion in these cortical areas was correlated with serum calcium and PTH levels. In two prospective studies of functional imaging, with SPECT [1] and fMRI [1], frontal reduced cerebral blood flow was found to be improved after parathyroidectomy, together with cognitive amelioration. There is a disagreement whether asymptomatic PHPT should be managed conservatively with surveillance, or with an early parathyroidectomy. According to the guidelines of the National Institutes of Health (NIH) for the management of asymptomatic PHPT [8,9], neurocognitive factors are integral to the diagnosis and treatment of PHPT, but should not constitute the sole indication for surgery. Some recent studies on the effect of surgery on cognitive symptoms in patients with PHPT showed that there was no significant improvement in cognitive deficits after successful parathyroidectomy [13,14,15]. However, other studies showed that surgical treatment appeared to improve some of these symptoms and afford benefit to the patients, quality of life [5,6,11]. The remarkable improvement of our patient post parathyroidectomy at all levels (Table 1) favours early parathyroidectomy in cases of PHPT with significant complications from CNS even in the absence of other symptoms of PHPT. In addition, our case suggests that, although rare, asymptomatic PHPT should be considered as a possible cause of dementia. References [1] Molaschi M, Ponzetto M, Romin R, et al. Neuropsychologic symptoms of primary hyperparathyroidism in the elderly. Report of a clinical case. Minerva Endocrinologica 1994;19:169–74.
[2] Joborn C, Hetta J, Frisk P, Palmer M, Akerstrom G, Ljunghall S. Primary hyperparathyroidism in patients with organic brain syndrome. Acta Medica Scandinavia 1986;219:91–8. [4] Silverberg SJ, Bilezikian JP. The diagnosis and management of asymptomatic primary hyperparathyroidism. Endocrinology & Metabolism 2006;2:494– 503. [5] Roman SA, Sosa JA, Mayes L, et al. Parathyroidectomy improves neurocognitive deficit in patients with primary hyperparathyroidism. Surgery 2005;138:1121–9. [6] Roman SA, Sosa JA. Psychiatric and cognitive aspects of primary hyperparathyroidism. Current Opinion in Oncology 2007;19:1–5. [7] Joborn C, Hetta J, Niklasson F, et al. Cerbrospinal fluid calcium, parathyroid hormone, and monoamine and purine metabolites and the blood–brain barrier function in primary hyperparathyroidism. Psychoneuroendocrinology 1991;16:311–22. [8] Cermik TF, Kaya M, Ugur-Altun B, et al. Regional cerebral blood flow abnormalities in patients with primary hyperparathyroidism. Neuroradiology 2007;49:379–85. [9] Mjaland O, Normann E, Halvorsen E, et al. Regional cerebral blood flow in patients with primary hyperparathyroidism before and after successful parathyroidectomy. British Journal of Surgery 2003;90:732–7. [10] Perrier ND, Coker LH, Rorie KD, et al. Preliminary report: functional MRI of the brain may be the ideal tool for evaluating neuropsychologic and sleep complaints of patients with primary hyperparathyroidism. World Journal of Surgery 2006;30:686–96. [11] Potts Jr JT, Fradkin JE, Aurbach GD, et al., editors. Proceedings of the NIH Consensus Development Conference on Diagnosis and Management of Asymptomatic Primary Hyperparathyroidism. J Bone Miner Res 1991;6:S1–166. [13] Prager G, Kalashek A, Kaczirek K, et al. Parathyroidectomy improved cognition and retentiveness in patients with primary hyperparathyroidism. Surgery 2002;132:930–6. [14] Dotzenrath CM, Kaetsch AK, Pfingsten H, et al. Neuropsychiatric and cognitive changes after surgery for primary hyperparathyroidism. World Journal of Surgery 2006;30:680–5. [15] Chiang CY, Andrewest DG, Anderson D, et al. A controlled, prospective study of neuropsychological outcomes post parathyroidectomy in primary hyperparathyroid patients. Clinical Endocrinology 2005;62:99–104.