Saturday, 6 August 2016

Clozapine Induced Neutropenia

Clozapine Induced Neutropenia

It has a risk of 2.7% in patients on clozapine. Fifty percent occur in the first 18 months. The risk is dose-independent, idiosyncratic like neuroleptic malignant syndrome. Risk of agranulocytosis is with clozapine is 0.8%.  

Risk factors: 

Afro-Caribbean ethnicity, early age, low baseline WCC

Mechanism: 

the mechanism of neutropenia and agranulocytosis is unclear

Friday, 5 August 2016

Dementia: An Overview & Recent Advances in Management

Dementia: An Overview & Recent Advances in Management

Prof. Arsalan Ahmad, Consultant Neurologist, Shifa International Hospital.

The Institute of Psychiatry, Benazir Bhutto Hospital, hosted a lecture on “Dementia: An Overview & Recent Advances in Management”, on the fourth of August 2016. The guest speaker was Prof. Arsalan Ahmad, the Consultant Neurologist at Shifa International Hospital. The audience included psychologists and residents and consultants from both neurology and psychiatry.

Prof. Fareed A. Minhas, Head of the Institute, set the stage for Prof. Arsalan’s lecture.  Part of our tradition, Prof. Minhas said, is to host these guest lectures. He alluded towards the overlap between psychiatry and neurology; many psychiatric patients present to neurologists and vice versa. Invariably, he said, a good evaluation would cause unveiling problems that require both neurological and psychiatric attention. He shared with the audience his satisfaction with the residents from the Shifa neurology department, especially their professionalism and knowledge base when they rotate at the Institute. He also appreciated Prof. Arsalan’s department for providing the psychiatry residents from BBH with an enlightening experience when they rotate there. He lamented the dearth of neurologists in our region, manifested because the Rawalpindi Medical College does not have any neurologists.  

He appreciated Prof. Arsalan’s efforts as President of the Neurology Society and the Movement Disorder Society. He reminded the young trainees in attendance that these affiliations are not possible without research contributions in high-affected factor journals globally. Turning to the importance of the topic, he said that over the next few years genetics would play a key role in psychiatry and neurology. This lecture, he emphasised, is an ideal opportunity for you to be introduced to the details thereof. Sadly, he said, we have precious little local research in this area.

He alluded to some research done in the area at the institute by Dr Asad Nizami, Assistant Professor at the Institute. As health care gets better people to survive to older age and thus dementias increase. The disability associated is severe. 
Neurology deals the brunt of it, and so Prof. Arsalan is the best man to update us on the topic.

Prof. Arsalan then began his presentation by thanking Prof. Fareed for the opportunity. He seconded the need for increased interaction between psychiatry and neurology. He reminded everyone of the joint conferences between neurology and psychiatry.  These have sadly dwindled over the years due to an increase in numbers of consultants and the patient burden. For an interdisciplinary relationship, he said, you must know your abilities and you must know your boundaries. He mentioned collaborations of his department with NUST and Quaid-e-Azam university and how that had led them to independently research with no international collaboration. This was not possible around a decade ago.  

Prof. Arsalan reminded everyone that dementia is a progressive deterioration in cognitive abilities with Alzheimer's being its most common type. It is a disease of the elderly and its risk doubles every five years after 65 years of age. As our population’s age, this would be an enormous burden, he remarked. They've increased the retirement age to reduce the burden of pensions etc. in the UK and our policymakers should be educated to make informed decisions.  

He alluded to the prevalence of the illness is 4.8 million in 2010 and how it would double to 9.5 million people by 2030, and 18 million in another 20 years.

For the lack of local data, he shared the prevalence rates in adjoining countries and using their estimates said that between 160,000 – 240,000 people may suffer from this illness in Pakistan. This, he said, would increase as life expectancy will increase.

He then spoke about the clinical features of the illness. In normal ageing, he said, people complain of forgetting, but if you ask them to focus, they may remember. In dementia, the family will complain that the patient is forgetful. Instrumental activities, he added, will deteriorate in dementia.

To diagnose he emphasised the importance of clinical and physical examination and psychological tools like the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) tool. He said that interpreting these tools should take education level, skills, language, and sensory impairments into consideration. He alluded to the greater sensitivity of MoCA in picking up dementias, especially in patients who are highly educated and those not educated at all.

He alerted the attendees to always look for pseudodementia; rule out other psychiatric illnesses to ensure appropriate patient care and referral to psychiatrists wherever necessary.  

Equally important, he said, is to rule out medical causes; of them, hypothyroidism and vitamin B-12 being the most common and treatable causes, especially in younger individuals.

He also highlighted the acute onset and underlying organic illness that distinguishes delirium from dementia.  

He also mentioned the importance of ruling out immune encephalitis. He enlightened the audience with the news that it is possible to diagnose and treat in our local setting. He gave the example of a patient from Multan with a three-month progressive cognitive decline and seizures suspected of CJD.

He had myoclonus like a jerk and a facial twitch. He had low serum sodium and EEG was normal. VGKc antibodies came out positive. He was given methylprednisolone and his condition dramatically improved, and he recovered.. What they called sporadic CJD, he said, is now being understood as immune encephalitis.

Dr Ayesha Minhas, Head of child psychiatry services at the institute, inquired about the immune encephalitis in children. Dr Arsalan said that the one with NMDAR ab can present in children. These children would have an awake encephalopathy. Their MRI would be normal, and EEG would encephalopathy. The symptoms would have an acute or sub-acute onset. The illness has a rapid progression and a paraneoplastic consequence of ovarian teratomas in young girls.

Prof. Arsalan also referred to drugs like antihistamines and digoxin etc. as a cause of memory impairment, and so that too should be ruled out. He spoke about the importance of diagnostic imaging to rule out treatable causes. 

He then spoke about genetics and genetic testing in dementias. They had identified the APP gene and PSEN 1 gene he said. PSEN1 causes younger-onset familial Alzheimer's he said.  

He raised the ethical dilemma associated with genetic testing whether the attendants would want to know about the illness. In an attempted study, only ten agreed to give samples. Here, he said, we have an opportunity for collaborative research. He also mentioned. APP A673 T as a possible protective gene and said that might explain how some people, even at ninety, are wonderful.

Despite the advances, he added, we do not recommend genetic testing and biomarkers since there is no definitive treatment.

He referred to new criteria for diagnosis for research participants and how that requires biomarkers. One biomarker that doesn’t require any invasive procedure is to assess the structural volume of hippocampus via MRI shows promise to be used in local studies as participants are not very willing for invasive procedures.

Prof. Arsalan then took the discussion towards management. The most crucial point, he said, was pharmacological treatment is symptomatic and no disease-modifying agent exists. It is important to inform the patients and their attendants of the realistic expectations from these drugs and to keep in mind their affordability while prescribing. He discussed the doses and side-effects of donepezil, rivastigmine, galantamine (recommended in mild-moderate illness), and memantine (recommended in moderate-severe illness).  

Speaking of the non-pharmacological interventions for prevention, he referred to many studies that showed no effect. One study, he said, entitled FINGER, showed that multi-domain approach (including dietary habits, active lifestyle, novelty-seeking, etc.) Showed the best preventive effect.

He also alluded to the patient safety issues that should be addressed; since the patients are cognitively compromised, they may get lost or harm themselves or others, so appropriate preventive measures need to be taken. Patients may require 24/7 home help, armbands for ID, and even GPS monitoring. The patients diagnosed early may need to be told to prepare their will or any other advanced directives they would want to leave behind.

In the questions and answer session, Dr Asad Nizami inquired what the people who have a family history of the illness should do. Prof. Arsalan acknowledged that’s a very grave issue and responded that a with an anecdotal account. He spoke about a patient who had dementia in her fifties and how her two children are living with the dread of getting this illness. One sibling in her forties says that she’s only planning for life till 50 years of age and her brother is continuously engaging in novel activities to prevent himself from acquiring the illness. Prof. Arsalan also shared his observation that he had not found a single hafiz in his dementia registry and hypothesised that that may be a possible preventive measure.   

Prof. Fareed Minhas concluded the lecture with a vote of thanks to the guest speaker. He also extended his gratitude to Mr Zeeshan, Mr Komail, and Mr Sohail from Lundbeck for collaborating for the arrangements of the lecture. With that, the participants were asked to gather for a group photograph and tea.  

Report by Dr Yousaf Raza, 4th Year Resident at the Institute of Psychiatry









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